Excerpt

Molecular Biology of the Cell is chiefly concerned with eucaryotic cells, as opposed to bacteria, and its title reflects the prime importance of the insights that have come from the molecular approach. Part I and Part II of the book analyze cells from this perspective and cover the traditional material of cell biology courses. But molecular biology by itself is not enough. The eucaryotic cells that form multicellular animals and plants are social organisms to an extreme degree: they live by cooperation and specialization. To understand how they function, one must study the ways cells in multicellular communities, as well as the internal workings of cells in isolation. These are two very different levels of investigation, but each depends on the other for focus and direction. We have therefore devoted Part III of the book to the behavior of cells in multicellular animals and plants. Thus developmental biology, histology, immunobiology, and neurobiology are discussed at much greater length than in other cell biology textbooks. While this material may be omitted from a basic cell biology course, serving as optimal or supplementary reading, it represents an essential part of our knowledge about cells and should be especially useful to those who decide to continue with biological or medical studies. The broad coverage expresses our conviction that cell biology should be at the center of a modern biological education.

Contents

• Part I. Introduction to the Cell
  • Chapter 1. The Evolution of the Cell
    • Introduction
    • From Molecules to the First Cell
      • Simple Biological Molecules Can Form Under Prebiotic Conditions
      • Complex Chemical Systems Can Develop in an Environment That Is Far from Chemical Equilibrium
      • Polynucleotides Are Capable of Directing Their Own Synthesis
      • Self-replicating Molecules Undergo Natural Selection
      • Specialized RNA Molecules Can Catalyze Biochemical Reactions
      • Information Flows from Polynucleotides to Polypeptides
      • Membranes Defined the First Cell
      • All Present-Day Cells Use DNA as Their Hereditary Material
      • Summary
    • From Procaryotes to Eucaryotes
      • Introduction
      • Procaryotic Cells Are Structurally Simple but Biochemically Diverse
      • Metabolic Reactions Evolve
      • Evolutionary Relationships Can Be Deduced by Comparing DNA Sequences
      • Cyanobacteria Can Fix CO₂ and N₂
      • Bacteria Can Carry Out the Aerobic Oxidation of Food Molecules
      • Eucaryotic Cells Contain Several Distinctive Organelles
      • Eucaryotic Cells Depend on Mitochondria for Their Oxidative Metabolism
      • Chloroplasts Are the Descendants of an Engulfed Procaryotic Cell
      • Eucaryotic Cells Contain a Rich Array of Internal Membranes
      • Eucaryotic Cells Have a Cytoskeleton
      • Protozoa Include the Most Complex Cells Known
      • In Eucaryotic Cells the Genetic Material Is Packaged in Complex Ways
      • Summary
    • From Single Cells to Multicellular Organisms
      • Introduction
      • Single Cells Can Associate to Form Colonies
      • The Cells of a Higher Organism Become Specialized and Cooperate
      • Multicellular Organization Depends on Cohesion Between Cells
      • Epithelial Sheets of Cells Enclose a Sheltered Internal Environment
      • Cell-Cell Communication Controls the Spatial Pattern of Multicellular Organisms
      • Cell Memory Permits the Development of Complex Patterns
      • Basic Developmental Programs Tend to Be Conserved in Evolution
      • The Cells of the Vertebrate Body Exhibit More Than 200 Different Modes of Specialization
      • Genes Can Be Switched On and Off
      • Sequence Comparisons Reveal Hundreds of Families of Homologous Genes
      • Summary
    • References
      • General
      • Cited
  • Chapter 2. Small Molecules, Energy, and Biosynthesis
    • Introduction
    • The Chemical Components of a Cell
      • Cell Chemistry Is Based on Carbon Compounds
      • Cells Use Four Basic Types of Small Molecules
      • Sugars Are Food Molecules of the Cell
      • Fatty Acids Are Components of Cell Membranes
      • Amino Acids Are the Subunits of Proteins
      • Nucleotides Are the Subunits of DNA and RNA
      • Summary
    • Biological Order and Energy
      • Introduction
      • Biological Order Is Made Possible by the Release of Heat Energy from Cells
      • Photosynthetic Organisms Use Sunlight to Synthesize Organic Compounds
      • Chemical Energy Passes from Plants to Animals
      • Cells Obtain Energy by the Oxidation of Biological Molecules
      • The Breakdown of an Organic Molecule Takes Place in a Sequence of Enzyme-catalyzed Reactions
      • Part of the Energy Released in Oxidation Reactions Is Coupled to the Formation of ATP
      • The Hydrolysis of ATP Generates Order in Cells
      • Summary
    • Food and the Derivation of Cellular Energy
      • Food Molecules Are Broken Down in Three Stages to Give ATP
      • Glycolysis Can Produce ATP Even in the Absence of Oxygen
      • NADH Is a Central Intermediate in Oxidative Catabolism
      • Metabolism Is Dominated by the Citric Acid Cycle
      • In Oxidative Phosphorylation the Transfer of Electrons to Oxygen Drives ATP Formation
      • Amino Acids and Nucleotides Are Part of the Nitrogen Cycle
      • Summary
    • Biosynthesis and the Creation of Order
      • Introduction
      • The Free-Energy Change for a Reaction Determines Whether It Can Occur
      • Biosynthetic Reactions Are Often Directly Coupled to ATP Hydrolysis
      • Coenzymes Are Involved in the Transfer of Specific Chemical Groups
      • The Structure of Coenzymes Suggests That They May Have Originated in an RNA World
      • Biosynthesis Requires Reducing Power
      • Biological Polymers Are Synthesized by Repetition of Elementary Dehydration Reactions
      • Summary
    • The Coordination of Catabolism and Biosynthesis
      • Metabolism Is Organized and Regulated
      • Metabolic Pathways Are Regulated by Changes in Enzyme Activity
      • Catabolic Reactions Can Be Reversed by an Input of Energy
      • Enzymes Can Be Switched On and Off by Covalent Modification
      • Reactions Are Compartmentalized Both Within Cells and Within Organisms
      • Summary
    • References
      • General
      • Cited
  • Chapter 3. Macromolecules: Structure, Shape, and Information
    • Introduction
    • Molecular Recognition Processes
      • Introduction
      • The Specific Interactions of a Macromolecule Depend on Weak, Noncovalent Bonds
      • A Helix Is a Common Structural Motif in Biological Structures Made from Repeated Subunits
      • Diffusion Is the First Step to Molecular Recognition
      • Thermal Motions Bring Molecules Together and Then Pull Them Apart
      • The Equilibrium Constant Is a Measure of the Strength of an Interaction Between Two Molecules
      • Atoms and Molecules Move Very Rapidly
      • Molecular Recognition Processes Can Never Be Perfect
      • Summary
    • Nucleic Acids
      • Genes Are Made of DNA
      • DNA Molecules Consist of Two Long Chains Held Together by Complementary Base Pairs
      • The Structure of DNA Provides an Explanation for Heredity
      • Errors in DNA Replication Cause Mutations
      • The Nucleotide Sequence of a Gene Determines the Amino Acid Sequence of a Protein
      • Portions of DNA Sequence Are Copied into RNA Molecules That Guide Protein Synthesis
      • Eucaryotic RNA Molecules Are Spliced to Remove Intron Sequences
      • Sequences of Nucleotides in mRNA Are "Read" in Sets of Three and Translated into Amino Acids
      • tRNA Molecules Match Amino Acids to Groups of Nucleotides
      • The RNA Message Is Read from One End to the Other by a Ribosome
      • Some RNA Molecules Function as Catalysts
      • Summary
    • Protein Structure
      • Introduction
      • The Shape of a Protein Molecule Is Determined by Its Amino Acid Sequence
      • Common Folding Patterns Recur in Different Protein Chains
      • Proteins Are Amazingly Versatile Molecules
      • Proteins Have Different Levels of Structural Organization
      • Domains Are Formed from a Polypeptide Chain That Winds Back and Forth, Making Sharp Turns at the Protein Surface
      • Relatively Few of the Many Possible Polypeptide Chains Would Be Useful
      • New Proteins Usually Evolve by Alterations of Old Ones
      • New Proteins Can Evolve by Recombining Preexisting Polypeptide Domains
      • Structural Homologies Can Help Assign Functions to Newly Discovered Proteins
      • Protein Subunits Can Assemble into Large Structures
      • A Single Type of Protein Subunit Can Interact with Itself to Form Geometrically Regular Assemblies
      • Coiled-Coil Proteins Help Build Many Elongated Structures in Cells
      • Proteins Can Assemble into Sheets, Tubes, or Spheres
      • Many Structures in Cells Are Capable of Self-assembly
      • Not All Biological Structures Form by Self-assembly
      • Summary
    • Proteins as Catalysts
      • Introduction
      • A Protein's Conformation Determines Its Chemistry
      • Substrate Binding Is the First Step in Enzyme Catalysis
      • Enzymes Speed Reactions by Selectively Stabilizing Transition States
      • Enzymes Can Promote the Making and Breaking of Covalent Bonds Through Simultaneous Acid and Base Catalysis
      • Enzymes Can Further Increase Reaction Rates by Forming Covalent Intermediates with Their Substrates
      • Enzymes Accelerate Chemical Reactions but Cannot Make Them Energetically More Favorable
      • Enzymes Determine Reaction Paths by Coupling Selected Reactions to ATP Hydrolysis
      • Multienzyme Complexes Help to Increase the Rate of Cell Metabolism
      • Summary
    • References
      • General
      • Cited
  • Chapter 4. How Cells Are Studied
    • Introduction
    • Looking at the Structure of Cells in the Microscope
      • Introduction
      • The Light Microscope Can Resolve Details 0.2 µm Apart
      • Tissues Are Usually Fixed and Sectioned for Microscopy
      • Different Components of the Cell Can Be Selectively Stained
      • Specific Molecules Can Be Located in Cells by Fluorescence Microscopy
      • Living Cells Are Seen Clearly in a Phase-Contrast or a Differential-Interference-Contrast Microscope
      • Images Can Be Enhanced and Analyzed by Electronic Techniques
      • Imaging of Complex Three-dimensional Objects Is Possible with the Confocal Scanning Microscope
      • The Electron Microscope Resolves the Fine Structure of the Cell
      • Biological Specimens Require Special Preparation for the Electron Microscope
      • Three-dimensional Images of Surfaces Can Be Obtained by Scanning Electron Microscopy
      • Metal Shadowing Allows Surface Features to Be Examined at High Resolution by Transmission Electron Microscopy
      • Freeze-Fracture and Freeze-Etch Electron Microscopy Provide Unique Views of the Cell Interior
      • Negative Staining and Cryoelectron Microscopy Allow Macromolecules to Be Viewed at High Resolution
      • Summary
    • Isolating Cells and Growing Them in Culture
      • Introduction
      • Cells Can Be Isolated from a Tissue and Separated into Different Types
      • Cells Can Be Grown in a Culture Dish
      • Serum-free, Chemically Defined Media Permit Identification of Specific Growth Factors
      • Eucaryotic Cell Lines Are a Widely Used Source of Homogeneous Cells
      • Cells Can Be Fused Together to Form Hybrid Cells
      • Summary
    • Fractionation of Cells and Analysis of Their Molecules
      • Introduction
      • Organelles and Macromolecules Can Be Separated by Ultracentrifugation
      • The Molecular Details of Complex Cellular Processes Can Be Deciphered in Cell-free Systems
      • Proteins Can Be Separated by Chromatography
      • The Size and Subunit Composition of a Protein Can Be Determined by SDS Polyacrylamide-Gel Electrophoresis
      • More Than 1000 Proteins Can Be Resolved on a Single Gel by Two-dimensional Polyacrylamide-Gel Electrophoresis
      • Selective Cleavage of a Protein Generates a Distinctive Set of Peptide Fragments
      • Short Amino Acid Sequences Can Be Analyzed by Automated Machines
      • The Diffraction of X-rays by Protein Crystals Can Reveal a Protein's Exact Structure
      • Molecular Structure Can Also Be Determined Using Nuclear Magnetic Resonance (NMR) Spectroscopy
      • Summary
    • Tracing and Assaying Molecules Inside Cells
      • Introduction
      • Radioactive Atoms Can Be Detected with Great Sensitivity
      • Radioisotopes Are Used to Trace Molecules in Cells and Organisms
      • Ion Concentrations Can Be Measured with Intracellular Electrodes
      • Rapidly Changing Intracellular Ion Concentrations Can Be Measured with Light-emitting Indicators
      • There Are Several Ways of Introducing Membrane-impermeant Molecules into Cells
      • The Light-induced Activation of "Caged" Precursor Molecules Facilitates Studies of Intracellular Dynamics
      • Antibodies Can Be Used to Detect and Isolate Specific Molecules
      • Hybridoma Cell Lines Provide a Permanent Source of Monoclonal Antibodies
      • Summary
    • References
      • General
      • Cited
• Part II. Molecular Genetics
  • Chapter 5. Protein Function
    • Introduction
    • Making Machines Out of Proteins
      • Introduction
      • The Binding of a Ligand Can Change the Shape of a Protein
      • Two Ligands That Bind to the Same Protein Often Affect Each Other's Binding
      • Two Ligands Whose Binding Sites Are Coupled Must Reciprocally Affect Each Other's Binding
      • Allosteric Transitions Help Regulate Metabolism
      • Proteins Often Form Symmetrical Assemblies That Undergo Cooperative Allosteric Transitions
      • The Allosteric Transition in Aspartate Transcarbamoylase Is Understood in Atomic Detail
      • Protein Phosphorylation Is a Common Way of Driving Allosteric Transitions in Eucaryotic Cells
      • A Eucaryotic Cell Contains Many Protein Kinases and Phosphatases
      • The Structure of Cdk Protein Kinase Shows How a Protein Can Function as a Microchip
      • Proteins That Bind and Hydrolyze GTP Are Ubiquitous Cellular Regulators
      • Other Proteins Control the Activity of GTP-binding Proteins by Determining Whether GTP or GDP Is Bound
      • The Allosteric Transition in EF-Tu Protein Shows How Large Movements Can Be Generated from Small Ones
      • Proteins That Hydrolyze ATP Do Mechanical Work in Cells
      • The Structure of Myosin Reveals How Muscles Exert Force
      • ATP-driven Membrane-bound Allosteric Proteins Can Either Act as Ion Pumps or Work in Reverse to Synthesize ATP
      • Energy-coupled Allosteric Transitions in Proteins Allow the Proteins to Function as Motors, Clocks, Assembly Factors, or Transducers of Information
      • Proteins Often Form Large Complexes That Function as Protein Machines
      • Summary
    • The Birth, Assembly, and Death of Proteins
      • Introduction
      • Proteins Are Thought to Fold Through a Molten Globule Intermediate
      • Molecular Chaperones Facilitate Protein Folding
      • Many Proteins Contain a Series of Independently Folded Modules
      • Modules Confer Versatility and Often Mediate Protein-Protein Interactions
      • Proteins Can Bind to Each Other Through Several Types of Interfaces
      • Linkage and Selective Proteolysis Ensure All-or-None Assembly
      • Ubiquitin-dependent Proteolytic Pathways Are Largely Responsible for Selective Protein Turnover in Eucaryotes
      • The Lifetime of a Protein Can Be Determined by Enzymes That Alter Its N-Terminus
      • Summary
    • References
      • General
      • Cited
  • Chapter 6. Basic Genetic Mechanisms
    • Introduction
    • RNA and Protein Synthesis
      • Introduction
      • RNA Polymerase Copies DNA into RNA: The Process of DNA Transcription
      • Only Selected Portions of a Chromosome Are Used to Produce RNA Molecules
      • Transfer RNA Molecules Act as Adaptors That Translate Nucleotide Sequences into Protein Sequences
      • Specific Enzymes Couple Each Amino Acid to Its Appropriate tRNA Molecule
      • Amino Acids Are Added to the Carboxyl-Terminal End of a Growing Polypeptide Chain
      • The Genetic Code Is Degenerate
      • The Events in Protein Synthesis Are Catalyzed on the Ribosome
      • A Ribosome Moves Stepwise Along the mRNA Chain
      • A Protein Chain Is Released from the Ribosome When Any One of Three Stop Codons Is Reached
      • The Initiation Process Sets the Reading Frame for Protein Synthesis
      • Only One Species of Polypeptide Chain Is Usually Synthesized from Each mRNA Molecule in Eucaryotes
      • The Binding of Many Ribosomes to an Individual mRNA Molecule Generates Polyribosomes
      • The Overall Rate of Protein Synthesis in Eucaryotes Is Controlled by Initiation Factors
      • The Fidelity of Protein Synthesis Is Improved by Two Proofreading Mechanisms
      • Many Inhibitors of Procaryotic Protein Synthesis Are Useful as Antibiotics
      • How Did Protein Synthesis Evolve?
      • Summary
    • DNA Repair
      • Introduction
      • DNA Sequences Are Maintained with Very High Fidelity
      • The Observed Mutation Rates in Proliferating Cells Are Consistent with Evolutionary Estimates
      • Most Mutations in Proteins Are Deleterious and Are Eliminated by Natural Selection
      • Low Mutation Rates Are Necessary for Life as We Know It
      • Low Mutation Rates Mean That Related Organisms Must Be Made from Essentially the Same Proteins
      • If Left Uncorrected, Spontaneous DNA Damage Would Rapidly Change DNA Sequences
      • The Stability of Genes Depends on DNA Repair
      • DNA Damage Can Be Removed by More Than One Pathway
      • Cells Can Produce DNA Repair Enzymes in Response to DNA Damage
      • The Structure and Chemistry of the DNA Double Helix Make It Easy to Repair
      • Summary
    • DNA Replication
      • Introduction
      • Base-pairing Underlies DNA Replication as well as DNA Repair
      • The DNA Replication Fork Is Asymmetrical
      • The High Fidelity of DNA Replication Requires a Proofreading Mechanism
      • Only DNA Replication in the 5'-to-3' Direction Allows Efficient Error Correction
      • A Special Nucleotide Polymerizing Enzyme Synthesizes Short RNA Primer Molecules on the Lagging Strand
      • Special Proteins Help Open Up the DNA Double Helix in Front of the Replication Fork
      • A Moving DNA Polymerase Molecule Is Kept Tethered to the DNA by a Sliding Ring
      • The Proteins at a Replication Fork Cooperate to Form a Replication Machine
      • A Mismatch Proofreading System Removes Replication Errors That Escape from the Replication Machine
      • Replication Forks Initiate at Replication Origins
      • DNA Topoisomerases Prevent DNA Tangling During Replication
      • DNA Replication Is Basically Similar in Eucaryotes and Procaryotes
      • Summary
    • Genetic Recombination
      • Introduction
      • General Recombination Is Guided by Base-pairing Interactions Between Complementary Strands of Two Homologous DNA Molecules
      • General Recombination Can Be Initiated at a Nick in One Strand of a DNA Double Helix
      • DNA Hybridization Reactions Provide a Simple Model for the Base-pairing Step in General Recombination
      • The RecA Protein Enables a DNA Single Strand to Pair with a Homologous Region of DNA Double Helix in E. coli
      • General Genetic Recombination Usually Involves a Cross-Strand Exchange
      • Gene Conversion Results from Combining General Recombination and Limited DNA Synthesis
      • Mismatch Proofreading Can Prevent Promiscuous Genetic Recombination Between Two Poorly Matched DNA Sequences
      • Site-specific Recombination Enzymes Move Special DNA Sequences into and out of Genomes
      • Transpositional Recombination Can Insert a Mobile Genetic Element into Any DNA Sequence
      • Summary
    • Viruses, Plasmids, and Transposable Genetic Elements
      • Introduction
      • Viruses Are Mobile Genetic Elements
      • The Outer Coat of a Virus May Be a Protein Capsid or a Membrane Envelope
      • Viral Genomes Come in a Variety of Forms and Can Be Either RNA or DNA
      • A Viral Chromosome Codes for Enzymes Involved in the Replication of Its Nucleic Acid
      • Both RNA Viruses and DNA Viruses Replicate Through the Formation of Complementary Strands
      • Viruses Exploit the Intracellular Traffic Machinery of their Host Cells
      • Different Enveloped Viruses Bud from Different Cellular Membranes
      • Viral Chromosomes Can Integrate into Host Chromosomes
      • The Continuous Synthesis of Some Viral Proteins Can Make Cells Cancerous
      • RNA Tumor Viruses Are Retroviruses
      • The Virus That Causes AIDS Is a Retrovirus
      • Some Transposable Elements Are Close Relatives of Retroviruses
      • Other Transposable Elements Transfer Themselves Directly from One Site in the Genome to Another
      • Most Viruses Probably Evolved from Plasmids
      • Summary
    • References
      • General
      • Cited
  • Chapter 7. Recombinant DNA Technology
    • Introduction
    • The Fragmentation, Separation, and Sequencing of DNA Molecules
      • Introduction
      • Restriction Nucleases Hydrolyze DNA Molecules at Specific Nucleotide Sequences
      • Restriction Maps Show the Distribution of Short Marker Nucleotide Sequences Along a Chromosome
      • Gel Electrophoresis Separates DNA Molecules of Different Sizes
      • Purified DNA Molecules Can Be Specifically Labeled with Radioisotopes or Chemical Markers in Vitro
      • Isolated DNA Fragments Can Be Rapidly Sequenced
      • DNA Footprinting Reveals the Sites Where Proteins Bind on a DNA Molecule
      • Summary
    • Nucleic Acid Hybridization
      • Introduction
      • Nucleic Acid Hybridization Reactions Provide a Sensitive Way of Detecting Specific Nucleotide Sequences
      • Northern and Southern Blotting Facilitate Hybridization with Electrophoretically Separated Nucleic Acid Molecules
      • RFLP Markers Greatly Facilitate Genetic Approaches to the Mapping and Analysis of Large Genomes
      • Synthetic DNA Molecules Facilitate the Prenatal Diagnosis of Genetic Diseases
      • Hybridization at Reduced Stringency Allows Even Distantly Related Genes to Be Identified
      • In Situ Hybridization Techniques Locate Specific Nucleic Acid Sequences in Cells or on Chromosomes
      • Summary
    • DNA Cloning
      • Introduction
      • A DNA Library Can Be Made Using Either Viral or Plasmid Vectors
      • Two Types of DNA Libraries Serve Different Purposes
      • cDNA Clones Contain Uninterrupted Coding Sequences
      • cDNA Libraries Can Be Prepared from Selected Populations of mRNA Molecules
      • Either a DNA Probe or a Test for Expressed Protein Can Be Used to Identify the Clones of Interest in a DNA Library
      • In Vitro Translation Facilitates Identification of the Correct DNA Clone
      • The Selection of Overlapping DNA Clones Allows One to "Walk" Along the Chromosome to a Nearby Gene of Interest
      • Ordered Genomic Clone Libraries Are Being Produced for Selected Organisms
      • Positional DNA Cloning Reveals Human Genes with Unanticipated Functions
      • Selected DNA Segments Can Be Cloned in a Test Tube by a Polymerase Chain Reaction
      • Summary
    • DNA Engineering
      • Introduction
      • New DNA Molecules of Any Sequence Can Be Formed by Joining Together DNA Fragments
      • Homogeneous RNA Molecules Can Be Produced in Large Quantities by DNA Transcription in Vitro
      • Rare Cellular Proteins Can Be Made in Large Amounts Using Expression Vectors
      • Reporter Genes Enable Regulatory DNA Sequences to Be Dissected
      • Mutant Organisms Best Reveal the Function of a Gene
      • Cells Containing Mutated Genes Can Be Made to Order
      • Genes Can Be Redesigned to Produce Proteins of Any Desired Sequence
      • Fusion Proteins Are Often Useful for Analyzing Protein Function
      • Normal Genes Can Be Easily Replaced by Mutant Ones in Bacteria and Some Lower Eucaryotes
      • Engineered Genes Can Be Used to Create Specific Dominant Mutations in Diploid Organisms
      • Engineered Genes Can Be Permanently Inserted into the Germ Line of Mice or Fruit Flies to Produce Transgenic Animals
      • Gene Targeting Makes It Possible to Produce Transgenic Mice That Are Missing Specific Genes
      • Transgenic Plants Are Important for Both Cell Biology and Agriculture
      • Summary
    • References
      • Cited
  • Chapter 8. The Cell Nucleus
    • Introduction
    • Chromosomal DNA and Its Packaging
      • Introduction
      • Each DNA Molecule That Forms a Linear Chromosome Must Contain a Centromere, Two Telomeres, and Replication Origins
      • Most Chromosomal DNA Does Not Code for Proteins or RNAs
      • Each Gene Produces an RNA Molecule
      • Comparisons Between the DNAs of Related Organisms Distinguish Conserved and Nonconserved Regions of DNA Sequence
      • Histones Are the Principal Structural Proteins of Eucaryotic Chromosomes
      • Histones Associate with DNA to Form Nucleosomes, the Unit Particles of Chromatin
      • The Positioning of Nucleosomes on DNA Is Determined by the Propensity of the DNA to Form Tight Loops and by the Presence of Other DNA-bound Proteins
      • Nucleosomes Are Usually Packed Together by Histone H1 to Form Regular Higher-Order Structures
      • Summary
    • The Global Structure of Chromosomes
      • Introduction
      • Lampbrush Chromosomes Contain Loops of Decondensed Chromatin
      • Orderly Domains of Interphase Chromatin Also Can Be Seen in Insect Polytene Chromosomes
      • Individual Chromatin Domains Can Unfold and Refold as a Unit
      • Both Bands and Interbands in Polytene Chromosomes Are Likely to Contain Genes
      • Transcriptionally Active Chromatin Is Less Condensed
      • Active Chromatin Is Biochemically Distinct
      • Heterochromatin Is Highly Condensed and Transcriptionally Inactive
      • Mitotic Chromosomes Are Formed from Chromatin in Its Most Condensed State
      • Each Mitotic Chromosome Contains a Characteristic Pattern of Very Large Domains
      • Summary
    • Chromosome Replication
      • Introduction
      • Specific DNA Sequences Serve as Replication Origins
      • A Mammalian Cell-free System Replicates the Chromosome of a Monkey Virus
      • Replication Origins Are Activated in Clusters on Higher Eucaryotic Chromosomes
      • Different Regions on the Same Chromosome Replicate at Distinct Times
      • Highly Condensed Chromatin Replicates Late, While Genes in Active Chromatin Replicate Early
      • The Late-replicating Replication Units Coincide with the A-T-rich Bands on Metaphase Chromosomes
      • The Controlled Timing of DNA Replication May Contribute to Cell Memory
      • Chromatin-bound Factors Ensure That Each Region of the DNA Is Replicated Only Once
      • New Histones Are Assembled into Chromatin as DNA Replicates
      • Telomeres Consist of Short G-rich Repeats That Are Added to Chromosome Ends by Telomerase
      • Summary
    • RNA Synthesis and RNA Processing
      • Introduction
      • RNA Polymerase Exchanges Subunits as It Begins Each RNA Chain
      • Three Kinds of RNA Polymerase Make RNA in Eucaryotes
      • RNA Polymerase II Transcribes Some DNA Sequences Much More Often Than Others
      • The Precursors of Messenger RNA Are Covalently Modified at Both Ends
      • RNA Processing Removes Long Nucleotide Sequences from the Middle of RNA Molecules
      • hnRNA Transcripts Are Immediately Coated with Proteins and snRNPs
      • Intron Sequences Are Removed as Lariat-shaped RNA Molecules
      • Multiple Intron Sequences Are Usually Removed from Each RNA Transcript
      • Studies of Thalassemia Reveal How RNA Splicing Can Allow New Proteins to Evolve
      • Spliceosome-catalyzed RNA Splicing Probably Evolved from Self-splicing Mechanisms
      • The Transport of mRNAs to the Cytoplasm Is Delayed Until Splicing Is Complete
      • Ribosomal RNAs (rRNAs) Are Transcribed from Tandemly Arranged Sets of Identical Genes
      • The Nucleolus Is a Ribosome-producing Machine
      • The Nucleolus Is a Highly Organized Subcompartment of the Nucleus
      • The Nucleolus Is Reassembled on Specific Chromosomes After Each Mitosis
      • Individual Chromosomes Occupy Discrete Territories in the Nucleus During Interphase
      • How Well Ordered Is the Nucleus?
      • Summary
    • The Organization and Evolution of the Nuclear Genome
      • Introduction
      • Genomes Are Fine-tuned by Point Mutation and Radically Remodeled or Enlarged by Genetic Recombination
      • Tandemly Repeated DNA Sequences Tend to Remain the Same
      • The Evolution of the Globin Gene Family Shows How Random DNA Duplications Contribute to the Evolution of Organisms
      • Genes Encoding New Proteins Can Be Created by the Recombination of Exons
      • Most Proteins Probably Originated from Highly Split Genes
      • A Major Fraction of the DNA of Higher Eucaryotes Consists of Repeated, Noncoding Nucleotide Sequences
      • Satellite DNA Sequences Have No Known Function
      • The Evolution of Genomes Has Been Accelerated by Transposable Elements
      • Transposable Elements Often Affect Gene Regulation
      • Transposition Bursts Cause Cataclysmic Changes in Genomes and Increase Biological Diversity
      • About 10% of the Human Genome Consists of Two Families of Transposable Elements
      • Summary
    • References
      • Cited
  • Chapter 9. Control of Gene Expression
    • Introduction
    • An Overview of Gene Control
      • Introduction
      • The Different Cell Types of a Multicellular Organism Contain the Same DNA
      • Different Cell Types Synthesize Different Sets of Proteins
      • A Cell Can Change the Expression of Its Genes in Response to External Signals
      • Gene Expression Can Be Regulated at Many of the Steps in the Pathway from DNA to RNA to Protein
      • Summary
    • DNA-binding Motifs in Gene Regulatory Proteins
      • Introduction
      • Gene Regulatory Proteins Were Discovered Using Bacterial Genetics
      • The Outside of the DNA Helix Can Be Read by Proteins
      • The Geometry of the DNA Double Helix Depends on the Nucleotide Sequence
      • Short DNA Sequences Are Fundamental Components of Genetic Switches
      • Gene Regulatory Proteins Contain Structural Motifs That Can Read DNA Sequences
      • The Helix-Turn-Helix Motif Is One of the Simplest and Most Common DNA-binding Motifs
      • Homeodomain Proteins Are a Special Class of Helix-Turn-Helix Proteins
      • There Are Several Types of DNA-binding Zinc Finger Motifs
      • β Sheets Can Also Recognize DNA
      • The Leucine Zipper Motif Mediates Both DNA Binding and Protein Dimerization
      • The Helix-Loop-Helix Motif Also Mediates Dimerization and DNA Binding
      • It Is Not Yet Possible to Predict the DNA Sequence Recognized by a Gene Regulatory Protein
      • A Gel-Mobility Shift Assay Allows Sequence-specific DNA-binding Proteins to Be Detected Readily
      • DNA Affinity Chromatography Facilitates the Purification of Sequence-specific DNA-binding Proteins
      • Summary
    • How Genetic Switches Work
      • Introduction
      • The Tryptophan Repressor Is a Simple Switch That Turns Genes On and Off in Bacteria
      • Transcriptional Activators Turn Genes On
      • A Transcriptional Activator and a Transcriptional Repressor Control the lac Operon
      • Regulation of Transcription in Eucaryotic Cells Is Complex
      • Eucaryotic RNA Polymerase Requires General Transcription Factors
      • Enhancers Control Genes at a Distance
      • A Eucaryotic Gene Control Region Consists of a Promoter Plus Regulatory DNA Sequences
      • Many Gene Activator Proteins Accelerate the Assembly of General Transcription Factors
      • Gene Repressor Proteins Can Inhibit Transcription in Various Ways
      • Eucaryotic Gene Regulatory Proteins Often Assemble into Small Complexes on DNA
      • Complex Genetic Switches That Regulate Drosophila Development Are Built Up from Smaller Modules
      • The Drosophila eve Gene Is Regulated by Combinatorial Controls
      • Complex Mammalian Gene Control Regions Are Also Constructed from Simple Regulatory Modules
      • The Activity of a Gene Regulatory Protein Can Itself Be Regulated
      • Bacteria Use Interchangeable RNA Polymerase Subunits to Help Regulate Gene Transcription
      • Gene Switches Have Gradually Evolved
      • Summary
    • Chromatin Structure and the Control of Gene Expression
      • Introduction
      • Transcription Can Be Activated on DNA That Is Packaged into Nucleosomes
      • Some Forms of Chromatin Silence Transcription
      • An Initial Decondensation Step May Be Required Before Mammalian Globin Genes Can Be Transcribed
      • The Mechanisms That Form Active Chromatin Are Not Understood
      • Superhelical Tension in DNA Allows Action at a Distance
      • Summary
    • The Molecular Genetic Mechanisms That Create Specialized Cell Types
      • Introduction
      • DNA Rearrangements Mediate Phase Variation in Bacteria
      • Several Gene Regulatory Proteins Determine Cell Type Identity in Yeasts
      • Two Proteins That Repress Each Other's Synthesis Determine the Heritable State of Bacteriophage Lambda
      • Expression of a Critical Gene Regulatory Protein Can Trigger Expression of a Whole Battery of Downstream Genes
      • Combinatorial Gene Control Is the Norm in Eucaryotes
      • An Inactive X Chromosome Is Inherited
      • Drosophila and Yeast Genes Can Also Be Inactivated by Heritable Features of Chromatin Structure
      • The Pattern of DNA Methylation Can Be Inherited When Vertebrate Cells Divide
      • DNA Methylation Reinforces Developmental Decisions in Vertebrate Cells
      • Genomic Imprinting Requires DNA Methylation
      • CG-rich Islands Are Associated with About 40,000 Genes in Mammals
      • Summary
    • Posttranscriptional Controls
      • Introduction
      • Transcription Attenuation Causes the Premature Termination of Some RNA Molecules
      • Alternative RNA Splicing Can Produce Different Forms of a Protein from the Same Gene
      • Sex Determination in Drosophila Depends on a Regulated Series of RNA Splicing Events
      • A Change in the Site of RNA Transcript Cleavage and Poly-A Addition Can Change the Carboxyl Terminus of a Protein
      • The Definition of a Gene Has Had to Be Modified Since the Discovery of Alternative RNA Splicing
      • RNA Transport from the Nucleus Can Be Regulated
      • Some mRNAs Are Localized to Specific Regions of the Cytoplasm
      • RNA Editing Can Change the Meaning of the RNA Message
      • Procaryotic and Eucaryotic Cells Use Different Strategies to Specify the Translation Start Site on an mRNA Molecule
      • The Phosphorylation of an Initiation Factor Regulates Protein Synthesis
      • Proteins That Bind to the 5' Leader Region of mRNAs Mediate Negative Translational Control
      • Gene Expression Can Be Controlled by a Change in mRNA Stability
      • Selective mRNA Degradation Is Coupled to Translation
      • Cytoplasmic Control of Poly-A Length Can Affect Translation in Addition to mRNA Stability
      • A Few mRNAs Contain a Recoding Signal That Interrupts the Normal Course of Translation
      • RNA-catalyzed Reactions in Cells Are Likely to Be of Extremely Ancient Origin
      • Summary
    • References
      • General
      • Cited
• Part III. Internal Organization of the Cell
  • Chapter 10. Membrane Structure
    • Introduction
    • The Lipid Bilayer
      • Introduction
      • Membrane Lipids Are Amphipathic Molecules, Most of Which Spontaneously Form Bilayers
      • The Lipid Bilayer Is a Two-dimensional Fluid
      • The Fluidity of a Lipid Bilayer Depends on Its Composition
      • The Lipid Bilayer Is Asymmetrical
      • Glycolipids Are Found on the Surface of All Plasma Membranes
      • Summary
    • Membrane Proteins
      • Introduction
      • Membrane Proteins Can Be Associated with the Lipid Bilayer in Various Ways
      • In Most Transmembrane Proteins the Polypeptide Chain Is Thought to Cross the Lipid Bilayer in an α-helical Conformation
      • Membrane Proteins Can Be Solubilized and Purified in Detergents
      • The Cytoplasmic Side of Membrane Proteins Can Be Readily Studied in Red Blood Cell Ghosts
      • Spectrin Is a Cytoskeletal Protein Noncovalently Associated with the Cytoplasmic Side of the Red Blood Cell Membrane
      • Glycophorin Extends Through the Red Blood Cell Lipid Bilayer as a Single α Helix
      • Band 3 of the Red Blood Cell Is a Multipass Membrane Protein That Catalyzes the Coupled Transport of Anions
      • Bacteriorhodopsin Is a Proton Pump That Traverses the Lipid Bilayer as Seven α Helices
      • Porins Are Pore-forming Transmembrane Proteins That Cross the Lipid Bilayer as a β Barrel
      • Membrane Proteins Often Function as Large Complexes
      • Many Membrane Proteins Diffuse in the Plane of the Membrane
      • Cells Can Confine Proteins and Lipids to Specific Domains Within a Membrane
      • The Cell Surface Is Coated with Sugar Residues
      • Selectins Are Cell-Surface Carbohydrate-binding Proteins That Mediate Transient Cell-Cell Adhesions in the Bloodstream
      • Summary
    • References
      • General
      • Cited
  • Chapter 11. Membrane Transport of Small Molecules and the Ionic Basis of Membrane Excitability
    • Introduction
    • Principles of Membrane Transport
      • Introduction
      • Protein - free Lipid Bilayers Are Highly Impermeable to Ions
      • There Are Two Main Classes of Membrane Transport Proteins - Carriers and Channels
      • Active Transport Is Mediated by Carrier Proteins Coupled to an Energy Source
      • Recombinant DNA Technology Has Revolutionized the Study of Membrane Transport Proteins
      • Ionophores Can Be Used as Tools to Increase the Permeability of Membranes to Specific Ions
      • Summary
    • Carrier Proteins and Active Membrane Transport
      • Introduction
      • The Plasma Membrane Na⁺-K⁺Pump Is an ATPase
      • The Na⁺-K⁺ ATPase Is Required to Maintain Osmotic Balance and Stabilize Cell Volume
      • Some Ca²⁺ Pumps Are Also Membrane-bound ATPases
      • Membrane-bound Enzymes That Synthesize ATP Are Transport ATPases Working in Reverse
      • Active Transport Can Be Driven by Ion Gradients
      • Na⁺-driven Carrier Proteins in the Plasma Membrane Regulate Cytosolic pH
      • An Asymmetrical Distribution of Carrier Proteins in Epithelial Cells Underlies the Transcellular Transport of Solutes
      • Some Bacterial Transport ATPases Are Homologous to Eucaryotic Transport ATPases Involved in Drug Resistance and Cystic Fibrosis: The ABC Transporter Superfamily
      • Summary
    • Ion Channels and Electrical Properties of Membranes
      • Introduction
      • Ion Channels Are Ion Selective and Fluctuate Between Open and Closed States
      • The Membrane Potential in Animal Cells Depends Mainly on K⁺ Leak Channels and the K⁺ Gradient Across the Plasma Membrane
      • The Resting Potential Decays Only Slowly When the Na⁺-K⁺ Pump Is Stopped
      • The Function of a Nerve Cell Depends on Its Elongated Structure
      • Voltage-gated Cation Channels Are Responsible for the Generation of Action Potentials in Electrically Excitable Cells
      • Myelination Increases the Speed and Efficiency of Action Potential Propagation in Nerve Cells
      • Patch-Clamp Recording Indicates That Individual Na⁺ Channels Open in an All-or-Nothing Fashion
      • Voltage-gated Cation Channels Are Evolutionarily and Structurally Related
      • Transmitter-gated Ion Channels Convert Chemical Signals into Electrical Ones at Chemical Synapses
      • Chemical Synapses Can Be Excitatory or Inhibitory
      • The Acetylcholine Receptors at the Neuromuscular Junction Are Transmitter-gated Cation Channels
      • Transmitter-gated Ion Channels Are Major Targets for Psychoactive Drugs
      • Neuromuscular Transmission Involves the Sequential Activation of Five Different Sets of Ion Channels
      • The Grand Postsynaptic Potential in a Neuron Represents a Spatial and Temporal Summation of Many Small Postsynaptic Potentials
      • Neuronal Computation Requires a Combination of At Least Three Kinds of K⁺ Channels
      • Long-term Potentiation in the Mammalian Hippocampus Depends on Ca²⁺ Entry Through NMDA-Receptor Channels
      • Summary
    • References
  • Chapter 12. Intracellular Compartments and Protein Sorting
    • Introduction
    • The Compartmentalization of Higher Cells
      • Introduction
      • All Eucaryotic Cells Have the Same Basic Set of Membrane-bounded Organelles
      • The Topological Relationships of Membrane-bounded Organelles Can Be Interpreted in Terms of Their Evolutionary Origins
      • Proteins Can Move Between Compartments in Different Ways
      • Signal Peptides and Signal Patches Direct Proteins to the Correct Cellular Address
      • Cells Cannot Construct Their Membrane-bounded Organelles de Novo: They Require Information in the Organelle Itself
      • Summary
    • The Transport of Molecules into and out of the Nucleus
      • Introduction
      • Nuclear Pores Perforate the Nuclear Envelope
      • Nuclear Localization Signals Direct Nuclear Proteins to the Nucleus
      • Macromolecules Are Actively Transported into and out of the Nucleus Through Nuclear Pores
      • The Nuclear Envelope Is Disassembled During Mitosis
      • Transport Between Nucleus and Cytosol Can Be Regulated by Preventing Access to the Transport Machinery
      • Summary
    • The Transport of Proteins into Mitochondria and Chloroplasts
      • Introduction
      • Translocation into the Mitochondrial Matrix Depends on a Matrix Targeting Signal
      • Translocation into the Mitochondrial Matrix Requires Both the Electrochemical Gradient Across the Inner Membrane and ATP Hydrolysis
      • Mitochondrial Proteins Are Imported into the Matrix in a Two-Stage Process at Contact Sites That Join the Inner and Outer Membranes
      • Proteins Are Imported into the Mitochondrial Matrix in an Unfolded State
      • Sequential Binding of the Imported Protein to Mitochondrial hsp70 and hsp60 Drives Its Translocation and Assists Protein Folding
      • Protein Transport into the Mitochondrial Inner Membrane and the Intermembrane Space Requires Two Signals
      • Two Signal Peptides Are Required to Direct Proteins to the Thylakoid Membrane in Chloroplasts
      • Summary
    • Peroxisomes
      • Introduction
      • Peroxisomes Use Molecular Oxygen and Hydrogen Peroxide to Carry Out Oxidative Reactions
      • A Short Signal Sequence Directs the Import of Proteins into Peroxisomes
      • Summary
    • The Endoplasmic Reticulum
      • Introduction
      • Membrane-bound Ribosomes Define the Rough ER
      • Smooth ER Is Abundant in Some Specialized Cells
      • Rough and Smooth Regions of ER Can Be Separated by Centrifugation
      • Signal Peptides Were First Discovered in Proteins Imported into the Rough ER
      • A Signal-Recognition Particle (SRP) Directs ER Signal Peptides to a Specific Receptor in the Rough ER Membrane
      • Translocation Across the ER Membrane Does Not Always Require Ongoing Polypeptide Chain Elongation
      • The Polypeptide Chain Passes Through an Aqueous Pore in the Translocation Apparatus
      • The ER Signal Peptide Is Removed from Most Soluble Proteins After Translocation
      • In Single-Pass Transmembrane Proteins a Single Internal ER Signal Peptide Remains in the Lipid Bilayer as a Membrane-spanning alpha Helix
      • Combinations of Start- and Stop-Transfer Signals Determine the Topology of Multipass Transmembrane Proteins
      • Translocated Polypeptide Chains Fold and Assemble in the Lumen of the Rough ER
      • Most Proteins Synthesized in the Rough ER Are Glycosylated by the Addition of a Common N-linked Oligosaccharide
      • Some Membrane Proteins Exchange a Carboxyl-Terminal Transmembrane Tail for a Covalently Attached Glycosylphosphatidylinositol (GPI) Anchor After Entry into the ER
      • Most Membrane Lipid Bilayers Are Assembled in the ER
      • Phospholipid Exchange Proteins Help Transport Phospholipids from the ER to Mitochondria and Peroxisomes
      • Summary
    • References
      • General
      • Cited
  • Chapter 13. Vesicular Traffic in the Secretory and Endocytic Pathways
    • Introduction
    • Transport from the ER Through the Golgi Apparatus
      • Introduction
      • The Golgi Apparatus Consists of an Ordered Series of Compartments
      • ER-Resident Proteins Are Selectively Retrieved from the Cis Golgi Network
      • Golgi Proteins Return to the ER When Cells Are Treated with the Drug Brefeldin A
      • Oligosaccharide Chains Are Processed in the Golgi Apparatus
      • The Golgi Cisternae Are Organized as a Series of Processing Compartments
      • Proteoglycans Are Assembled in the Golgi Apparatus
      • The Carbohydrate in Cell Membranes Faces the Side of the Membrane That Is Topologically Equivalent to the Outside of the Cell
      • What Is the Purpose of Glycosylation?
      • Summary
    • Transport from the Trans Golgi Network to Lysosomes
      • Introduction
      • Lysosomes Are the Principal Sites of Intracellular Digestion
      • Lysosomes Are Heterogeneous
      • Plant and Fungal Vacuoles Are Remarkably Versatile Lysosomes
      • Materials Are Delivered to Lysosomes by Multiple Pathways
      • Some Cytosolic Proteins Are Directly Transported into Lysosomes for Degradation
      • Lysosomal Enzymes Are Sorted from Other Proteins in the Trans Golgi Network by a Membrane-bound Receptor Protein That Recognizes Mannose 6-Phosphate
      • The Mannose 6-Phosphate Receptor Shuttles Back and Forth Between Specific Membranes
      • A Signal Patch in the Polypeptide Chain Provides the Cue for Tagging a Lysosomal Enzyme with Mannose 6-Phosphate
      • Defects in the GlcNAc Phosphotransferase Cause a Lysosomal Storage Disease in Humans
      • Summary
    • Transport from the Plasma Membrane via Endosomes: Endocytosis
      • Introduction
      • Specialized Phagocytic Cells Can Ingest Large Particles
      • Pinocytic Vesicles Form from Coated Pits in the Plasma Membrane
      • Clathrin-coated Pits Can Serve as a Concentrating Device for Internalizing Specific Extracellular Macromolecules
      • Cells Import Cholesterol by Receptor-mediated Endocytosis
      • Endocytosed Materials Often End Up in Lysosomes
      • Specific Proteins Are Removed from Early Endosomes and Returned to the Plasma Membrane
      • The Relationship Between Early and Late Endosomes Is Uncertain
      • Macromolecules Can Be Transferred Across Epithelial Cell Sheets by Transcytosis
      • Epithelial Cells Have Two Distinct Early Endosomal Compartments But a Common Late Endosomal Compartment
      • Summary
    • Transport from the Trans Golgi Network to the Cell Surface: Exocytosis
      • Introduction
      • Many Proteins and Lipids Seem to Be Carried Automatically from the ER and Golgi Apparatus to the Cell Surface
      • Secretory Vesicles Bud from the Trans Golgi Network
      • Proteins Are Often Proteolytically Processed During the Formation of Secretory Vesicles
      • Secretory Vesicles Wait Near the Plasma Membrane Until Signaled to Release Their Contents
      • Regulated Exocytosis Is a Localized Response of the Plasma Membrane and Its Underlying Cytoplasm
      • Secretory-Vesicle Membrane Components Are Recycled
      • Synaptic Vesicles Form from Endosomes
      • Polarized Cells Direct Proteins from the Trans Golgi Network to the Appropriate Domain of the Plasma Membrane
      • Summary
    • The Molecular Mechanisms of Vesicular Transport and the Maintenance of Compartmental Diversity
      • Introduction
      • Maintenance of Differences Between Compartments Requires an Input of Free Energy
      • There Is More Than One Type of Coated Vesicle
      • The Assembly of a Clathrin Coat Drives Bud Formation
      • Adaptins Recognize Specific Transmembrane Proteins and Link Them to the Clathrin Cage
      • Coatomer-coated Vesicles Mediate Nonselective Vesicular Transport
      • Vesicular Transport Depends on Regulatory GTP-binding Proteins
      • ARF Seems to Signal the Assembly and Disassembly of the Coatomer Coat
      • Organelle Marker Proteins Called SNAREs Help Guide Vesicular Transport
      • Rab Proteins Are Thought to Ensure the Specificity of Vesicle Docking
      • Vesicle Fusion Is Catalyzed by a "Membrane-Fusion Machine"
      • The Best-characterized Membrane-Fusion Protein Is Made by a Virus
      • Summary
    • References
      • General
      • Cited
  • Chapter 14. Energy Conversion: Mitochondria and Chloroplasts
    • Introduction
    • The Mitochondrion
      • Introduction
      • The Mitochondrion Contains an Outer Membrane and an Inner Membrane That Create Two Internal Compartments
      • Mitochondrial Oxidation Begins When Large Amounts of Acetyl CoA Are Produced in the Matrix Space from Fatty Acids and Pyruvate
      • The Citric Acid Cycle Oxidizes the Acetyl Group on Acetyl CoA to Generate NADH and FADH₂ for the Respiratory Chain
      • A Chemiosmotic Process Converts Oxidation Energy into ATP on the Inner Mitochondrial Membrane
      • Electrons Are Transferred from NADH to Oxygen Through Three Large Respiratory Enzyme Complexes
      • Energy Released by the Passage of Electrons Along the Respiratory Chain Is Stored as an Electrochemical Proton Gradient Across the Inner Membrane
      • The Energy Stored in the Electrochemical Proton Gradient Is Used to Produce ATP and to Transport Metabolites and Inorganic Ions into the Matrix Space
      • The Rapid Conversion of ADP to ATP in Mitochondria Maintains a High Ratio of ATP to ADP in Cells
      • The Difference Between Δ G° and Δ G: A Large Negative Value of Δ G Is Required for ATP Hydrolysis to Be Useful to the Cell
      • Cellular Respiration Is Remarkably Efficient
      • Summary
    • The Respiratory Chain and ATP Synthase
      • Introduction
      • Functional Inside-out Particles Can Be Isolated from Mitochondria
      • ATP Synthase Can Be Purified and Added Back to Membranes
      • ATP Synthase Can Function in Reverse to Hydrolyze ATP and Pump H⁺
      • The Respiratory Chain Pumps H⁺ Across the Inner Mitochondrial Membrane
      • Spectroscopic Methods Have Been Used to Identify Many Electron Carriers in the Respiratory Chain
      • The Respiratory Chain Contains Three Large Enzyme Complexes Embedded in the Inner Membrane
      • An Iron-Copper Center in Cytochrome Oxidase Catalyzes Efficient O₂ Reduction
      • Electron Transfers Are Mediated by Random Collisions Between Diffusing Donors and Acceptors in the Mitochondrial Inner Membrane
      • A Large Drop in Redox Potential Across Each of the Three Respiratory Enzyme Complexes Provides the Energy for H⁺ Pumping
      • The Mechanism of H⁺ Pumping Is Best Understood in Bacteriorhodopsin
      • H⁺ Ionophores Dissipate the H⁺ Gradient and Thereby Uncouple Electron Transport from ATP Synthesis
      • Respiratory Control Normally Restrains Electron Flow Through the Chain
      • Natural Uncouplers Convert the Mitochondria in Brown Fat into Heat-generating Machines
      • All Bacteria Use Chemiosmotic Mechanisms to Harness Energy
      • Summary
    • Chloroplasts and Photosynthesis
      • Introduction
      • The Chloroplast Is One Member of a Family of Organelles That Is Unique to Plants - the Plastids
      • Chloroplasts Resemble Mitochondria But Have an Extra Compartment
      • Two Unique Reactions in Chloroplasts: The Light-driven Production of ATP and NADPH and the Conversion of CO₂ to Carbohydrate
      • Carbon Fixation Is Catalyzed by Ribulose Bisphosphate Carboxylase
      • Three Molecules of ATP and Two Molecules of NADPH Are Consumed for Each CO₂ Molecule That Is Fixed in the Carbon-Fixation Cycle
      • Carbon Fixation in Some Plants Is Compartmentalized to Facilitate Growth at Low CO₂ Concentrations
      • Photosynthesis Depends on the Photochemistry of Chlorophyll Molecules
      • A Photosystem Contains a Reaction Center Plus an Antenna Complex
      • In a Reaction Center, Light Energy Captured by Chlorophyll Creates a Strong Electron Donor from a Weak One
      • In Plants and Cyanobacteria Noncyclic Photophosphorylation Produces Both NADPH and ATP
      • Chloroplasts Can Make ATP by Cyclic Photophosphorylation Without Making NADPH
      • The Electrochemical Proton Gradient Is Similar in Mitochondria and Chloroplasts
      • Like the Mitochondrial Inner Membrane, the Chloroplast Inner Membrane Contains Carrier Proteins That Facilitate Metabolite Exchange with the Cytosol
      • Chloroplasts Carry Out Other Biosyntheses
      • Summary
    • The Evolution of Electron-Transport Chains
      • Introduction
      • The Earliest Cells Probably Produced ATP by Fermentation
      • The Evolution of Energy-conserving Electron-transport Chains Enabled Anaerobic Bacteria to Use Non-fermentable Organic Compounds as a Source of Energy
      • By Providing an Inexhaustible Source of Reducing Power, Photosynthetic Bacteria Overcame a Major Obstacle in the Evolution of Cells
      • The More Complex Photosynthetic Electron-Transport Chains of Cyanobacteria Produced Atmospheric Oxygen and Permitted New Life Forms
      • Summary
    • The Genomes of Mitochondria and Chloroplasts
      • Introduction
      • The Biosynthesis of Mitochondria and Chloroplasts Involves the Contribution of Two Separate Genetic Systems
      • Organelle Growth and Division Maintain the Number of Mitochondria and Chloroplasts in a Cell
      • The Genomes of Chloroplasts and Mitochondria Are Usually Circular DNA Molecules
      • Mitochondria and Chloroplasts Contain Complete Genetic Systems
      • The Chloroplast Genome of Higher Plants Contains About 120 Genes
      • Mitochondrial Genomes Have Several Surprising Features
      • Animal Mitochondria Contain the Simplest Genetic Systems Known
      • Why Are Plant Mitochondrial Genomes So Large?
      • Some Organelle Genes Contain Introns
      • Mitochondrial Genes Can Be Distinguished from Nuclear Genes by Their Non-Mendelian (Cytoplasmic) Inheritance
      • Organelle Genes Are Maternally Inherited in Many Organisms
      • Petite Mutants in Yeasts Demonstrate the Overwhelming Importance of the Cell Nucleus for Mitochondrial Biogenesis
      • Mitochondria and Chloroplasts Contain Tissue-specific Proteins
      • Mitochondria Import Most of Their Lipids; Chloroplasts Make Most of Theirs
      • Both Mitochondria and Chloroplasts Probably Evolved from Endosymbiotic Bacteria
      • Why Do Mitochondria and Chloroplasts Have Their Own Genetic Systems?
      • Summary
    • References
      • General
      • Cited
  • Chapter 15. Cell Signaling
    • Introduction
    • General Principles of Cell Signaling
      • Introduction
      • Extracellular Signaling Molecules Are Recognized by Specific Receptors on or in Target Cells
      • Secreted Molecules Mediate Three Forms of Signaling: Paracrine, Synaptic, and Endocrine
      • Autocrine Signaling Can Coordinate Decisions by Groups of Identical Cells
      • Gap Junctions Allow Signaling Information to Be Shared by Neighboring Cells
      • Each Cell Is Programmed to Respond to Specific Combinations of Signaling Molecules
      • Different Cells Can Respond Differently to the Same Chemical Signal
      • The Concentration of a Molecule Can Be Adjusted Quickly Only If the Lifetime of the Molecule Is Short
      • Nitric Oxide Gas Signals by Binding Directly to an Enzyme Inside the Target Cell
      • Steroid Hormones, Thyroid Hormones, Retinoids, and Vitamin D Bind to Intracellular Receptors That Are Ligand-activated Gene Regulatory Proteins
      • There Are Three Known Classes of Cell-Surface Receptor Proteins: Ion-Channel-linked, G-Protein-linked, and Enzyme-linked
      • Activated Cell-Surface Receptors Trigger Phosphate-Group Additions to a Network of Intracellular Proteins
      • Summary
    • Signaling via G-Protein-linked Cell-Surface Receptors
      • Introduction
      • Trimeric G Proteins Relay the Intracellular Signal from G-Protein-linked Receptors
      • Some Receptors Increase Intracellular Cyclic AMP by Activating Adenylyl Cyclase via a Stimulatory G Protein (G_s)
      • Trimeric G Proteins Are Thought to Disassemble When Activated
      • Some Receptors Decrease Cyclic AMP by Inhibiting Adenylyl Cyclase via an Inhibitory Trimeric G Protein (G_i)
      • Cyclic-AMP-dependent Protein Kinase (A-Kinase) Mediates the Effects of Cyclic AMP
      • Serine/Threonine Protein Phosphatases Rapidly Reverse the Effects of A-Kinase
      • To Use Ca²⁺ as an Intracellular Signal, Cells Must Keep Resting Cytosolic Ca²⁺ Levels Low
      • Ca²⁺ Functions as a Ubiquitous Intracellular Messenger
      • Some G-Protein-linked Receptors Activate the Inositol Phospholipid Signaling Pathway by Activating Phospholipase C-β
      • Inositol Trisphosphate (IP₃) Couples Receptor Activation to Ca²⁺ Release from the ER
      • Ca²⁺ Oscillations Often Prolong the Initial IP₃-induced Ca²⁺ Response
      • Diacylglycerol Activates Protein Kinase C (C-Kinase)
      • Calmodulin Is a Ubiquitous Intracellular Ca²⁺ Receptor
      • Ca²⁺/Calmodulin-dependent Protein Kinases (CaM-Kinases) Mediate Most of the Actions of Ca²⁺ in Animal Cells
      • The Cyclic AMP and Ca²⁺ Pathways Interact
      • Some Trimeric G Proteins Directly Regulate Ion Channels
      • Smell and Vision Depend on G-Protein-linked Receptors and Cyclic-Nucleotide-gated Ion Channels
      • Extracellular Signals Are Greatly Amplified by the Use of Intracellular Mediators and Enzymatic Cascades
      • Cells Can Respond Suddenly to a Gradually Increasing Concentration of an Extracellular Signal
      • The Effect of Some Signals Can Be Remembered by the Cell
      • Summary
    • Signaling via Enzyme-linked Cell-Surface Receptors
      • Introduction
      • Receptor Guanylyl Cyclases Generate Cyclic GMP Directly
      • The Receptors for Most Growth Factors Are Transmembrane Tyrosine-specific Protein Kinases
      • Phosphorylated Tyrosine Residues Are Recognized by Proteins with SH2 Domains
      • The Ras Proteins Provide a Crucial Link in the Intracellular Signaling Cascades Activated by Receptor Tyrosine Kinases
      • An SH Adaptor Protein Couples Receptor Tyrosine Kinases to Ras: Evidence from the Developing Drosophila Eye
      • Ras Activates a Serine/Threonine Phosphorylation Cascade That Activates MAP-Kinase
      • Tyrosine-Kinase-associated Receptors Depend on Nonreceptor Tyrosine Kinases for Their Activity
      • Some Receptors Are Protein Tyrosine Phosphatases
      • Cancer-promoting Oncogenes Have Helped Identify Many Components in the Receptor Tyrosine Kinase Signaling Pathways
      • Proteins in the TGF-β Superfamily Activate Receptors That Are Serine/Threonine Protein Kinases
      • The Notch Transmembrane Receptor Mediates Lateral Inhibition by an Unknown Mechanism
      • Summary
    • Target-Cell Adaptation
      • Introduction
      • Slow Adaptation Depends on Receptor Down-Regulation
      • Rapid Adaptation Often Involves Receptor Phosphorylation
      • Some Forms of Adaptation Are Due to Downstream Changes
      • Adaptation Plays a Crucial Role in Bacterial Chemotaxis
      • Bacterial Chemotaxis Is Mediated by a Family of Four Homologous Transmembrane Receptors and a Phosphorylation Relay System
      • Receptor Methylation Is Responsible for Adaptation in Bacterial Chemotaxis
      • Summary
    • The Logic of Intracellular Signaling: Lessons from Computer-based "Neural Networks"
      • Introduction
      • Computer-based Neural Networks Can Be Trained
      • Cell Signaling Networks Can Be Viewed as Neural Networks Trained by Evolution
      • Signaling Networks Enable Cells to Respond to Complex Patterns of Extracellular Signals
      • Signaling Networks Are Robust
      • Summary
    • References
      • General
      • Cited
  • Chapter 16. The Cytoskeleton
    • Introduction
    • The Nature of the Cytoskeleton
      • Introduction
      • The Cytoplasm of a Eucaryotic Cell Is Spatially Organized by Actin Filaments, Microtubules, and Intermediate Filaments
      • Dynamic Microtubules Emanate from the Centrosome
      • The Microtubule Network Can Find the Center of the Cell
      • Motor Proteins Use the Microtubule Network as a Scaffold to Position Membrane-bounded Organelles
      • The Actin Cortex Can Generate and Maintain Cell Polarity
      • Actin Filaments and Microtubules Usually Act Together to Polarize the Cell
      • The Functions of the Cytoskeleton Are Difficult to Study
      • Summary
    • Intermediate Filaments
      • Introduction
      • Intermediate Filaments Are Polymers of Fibrous Proteins
      • Epithelial Cells Contain a Highly Diverse Family of Keratin Filaments
      • Many Nonepithelial Cells Contain Their Own Distinctive Cytoplasmic Intermediate Filaments
      • The Nuclear Lamina Is Constructed from a Special Class of Intermediate Filament Proteins - the Lamins
      • Intermediate Filaments Provide Mechanical Stability to Animal Cells
      • Summary
    • Microtubules
      • Introduction
      • Microtubules Are Hollow Tubes Formed from Tubulin
      • Microtubules Are Highly Labile Structures That Are Sensitive to Specific Antimitotic Drugs
      • Elongation of a Microtubule Is Rapid, Whereas the Nucleation of a New Microtubule Is Slow
      • The Two Ends of a Microtubule Are Different and Grow at Different Rates
      • Centrosomes Are the Primary Site of Nucleation of Microtubules in Animal Cells
      • Microtubules Depolymerize and Repolymerize Continually in Animal Cells
      • GTP Hydrolysis Can Explain the Dynamic Instability of Individual Microtubules
      • The Dynamic Instability of Microtubules Provides an Organizing Principle for Cell Morphogenesis
      • Microtubules Undergo a Slow "Maturation" Revealed by Posttranslational Modifications of Their Tubulin
      • Microtubule-associated Proteins (MAPs) Bind to Microtubules and Modify Their Properties
      • MAPs Help Create Functionally Differentiated Cytoplasm
      • Kinesin and Dynein Direct Organelle Movement Along Microtubules
      • The Rate and Direction of Movement Along a Microtubule Are Specified by the Head Domain of Motor Proteins
      • Summary
    • Cilia and Centrioles
      • Introduction
      • Cilia Move by the Bending of an Axoneme - a Complex Bundle of Microtubules
      • Dynein Drives the Movements of Cilia and Flagella
      • Flagella and Cilia Grow from Basal Bodies That Are Closely Related to Centrioles
      • Centrioles Usually Arise by the Duplication of Preexisting Centrioles
      • Summary
    • Actin Filaments
      • Introduction
      • Actin Filaments Are Thin and Flexible
      • Actin and Tubulin Polymerize by Similar Mechanisms
      • ATP Hydrolysis Is Required for the Dynamic Behavior of Actin Filaments
      • The Functions of Actin Filaments Are Inhibited by Both Polymer-stabilizing and Polymer-destabilizing Drugs
      • The Actin Molecule Binds to Small Proteins That Help to Control Its Polymerization
      • Many Cells Extend Dynamic Actin-containing Microspikes and Lamellipodia from Their Leading Edge
      • The Leading Edge of Motile Cells Nucleates Actin Polymerization
      • Some Pathogenic Bacteria Use Actin to Move Within and Between Cells
      • Polymerization of Actin in the Cell Cortex Is Controlled by Cell-Surface Receptors
      • Heterotrimeric G Proteins and Small GTPases Relay Signals from the Cell Surface to the Actin Cortex
      • Mechanisms of Cell Polarization Can Be Analyzed in Yeast Cells
      • Summary
    • Actin-binding Proteins
      • Introduction
      • A Simple Membrane-attached Cytoskeleton Provides Mechanical Support to the Plasma Membrane of Erythrocytes
      • Cross-linking Proteins with Different Properties Organize Particular Actin Assemblies
      • Actin-binding Proteins with Different Properties Are Built Up from Similar Modules
      • Gelsolin Fragments Actin Filaments in Response to Ca²⁺ Activation
      • Multiple Types of Myosin Are Found in Eucaryotic Cells
      • There Are Transient Musclelike Assemblies in Nonmuscle Cells
      • Focal Contacts Allow Actin Filaments to Pull Against the Substratum
      • Microvilli Illustrate How Bundles of Cross-linked Actin Filaments Can Stabilize Local Extensions of the Plasma Membrane
      • The Behavior of the Cell Cortex Depends on a Balance of Cooperative and Competitive Interactions Among a Large Set of Actin-binding Proteins
      • The Migration of Animal Cells Can Be Divided into Three Distinct Actin-dependent Subprocesses
      • The Mechanism of Cell Locomotion Can Be Dissected Genetically
      • Summary
    • Muscle
      • Introduction
      • Myofibrils Are Composed of Repeating Assemblies of Thick and Thin Filaments
      • Contraction Occurs as the Myosin and Actin Filaments Slide Past Each Other
      • A Myosin Head "Walks" Toward the Plus End of an Actin Filament
      • Muscle Contraction Is Initiated by a Sudden Rise in Cytosolic Ca²⁺
      • Troponin and Tropomyosin Mediate the Ca²⁺ Regulation of Skeletal Muscle Contraction
      • Other Accessory Proteins Maintain the Architecture of the Myofibril and Provide It with Elasticity
      • The Same Contractile Machinery, in Modified Form, Is Found in Heart Muscle and Smooth Muscle
      • The Activation of Myosin in Many Cells Depends on Myosin Light-Chain Phosphorylation
      • Summary
    • References
      • General
      • Cited
  • Chapter 17. The Cell-Division Cycle
    • Introduction
    • The General Strategy of the Cell Cycle
      • Introduction
      • Replication of the Nuclear DNA Occurs During a Specific Part of Interphase - the S Phase
      • Discrete Cell-Cycle Events Occur Against a Background of Continuous Growth
      • A Central Control System Triggers the Essential Processes of the Cell Cycle
      • The Cell-Cycle Control System Is a Protein-Kinase-based Machine
      • Summary
    • The Early Embryonic Cell Cycle and the Role of MPF
      • Introduction
      • Growth of the Xenopus Oocyte Is Balanced by Cleavage of the Egg
      • A Cytoplasmic Regulator, MPF, Controls Entry into Mitosis
      • Oscillations in MPF Activity Control the Cell-Division Cycle
      • Cyclin Accumulation and Destruction Control the Activation and Inactivation of MPF
      • Degradation of Cyclin Triggers Exit from Mitosis
      • MPF Can Act Autocatalytically to Stimulate Its Own Activation
      • Active MPF Induces the Downstream Events of Mitosis
      • The Cell-Cycle Control System Allows Time for One Round of DNA Replication in Each Interphase
      • A Re-replication Block Ensures That No Segment of DNA Is Replicated More Than Once in a Cell Cycle
      • Passage Through Mitosis Removes the Re-replication Block
      • Summary
    • Yeasts and the Molecular Genetics of Cell-Cycle Control
      • Introduction
      • Cell Growth Requires a Prolonged Interphase with Cell-Cycle Checkpoints
      • Fission and Budding Yeasts Change Their Shape as They Progress Around the Cell Cycle
      • Cell-Division-Cycle Mutations Halt the Cycle at Specific Points; wee Mutations Let the Cycle Skip Past a Size Checkpoint
      • The Subunits of MPF in Yeasts Are Homologous to Those of MPF in Animals
      • MPF Activity Is Regulated by Phosphorylation and Dephosphorylation
      • The MPF-Activation Mechanism Controls Size in Fission Yeast
      • For Most Cells the Major Cell-Cycle Checkpoint Is in G₁ at Start
      • The Cdc2 Protein Associates with G₁ Cyclins to Drive a Cell Past Start
      • The G₁ Cyclins Mediate Multiple Controls That Operate at Start
      • Start Kinase Triggers Production of Components Required for DNA Replication
      • Feedback Controls Ensure That Cells Complete One Cell-Cycle Process Before They Start the Next
      • Damaged DNA Generates a Signal to Delay Mitosis
      • Feedback Controls in the Cell Cycle Generally Depend on Inhibitory Signals
      • Summary
    • Cell-Division Controls in Multicellular Animals
      • Introduction
      • The Mammalian Cell-Cycle Control System Is More Elaborate Than That of the Yeast
      • The Regulation of Mammalian Cell Growth and Proliferation Is Commonly Studied in Cultured Cell Lines
      • Growth Factors Stimulate the Proliferation of Mammalian Cells
      • Cell Growth and Cell Division Can Be Independently Regulated
      • Cells Can Delay Division by Entering a Specialized Nongrowing State
      • Serum Deprivation Prevents Passage Through the G₁ Checkpoint
      • The Cell-Cycle Control System Can Be Rapidly Disassembled But Only Slowly Reassembled
      • Neighboring Cells Compete for Growth Factors
      • Normal Animal Cells in Culture Need Anchorage in Order to Pass Start
      • Studies of Cancer Cells Reveal Genes Involved in the Control of Cell Proliferation
      • Growth Factors Trigger Cascades of Intracellular Signals
      • Cyclins and Cdk Are Induced by Growth Factor After a Long Delay
      • The Retinoblastoma Protein Acts to Hold Proliferation in Check
      • The Probability of Entering G₀ Increases with the Number of Times That a Cell Divides: Cell Senescence
      • Intricately Regulated Patterns of Cell Division Generate and Maintain the Body
      • Summary
    • References
      • General
      • Cited
  • Chapter 18. The Mechanics of Cell Division
    • Introduction
    • An Overview of M Phase
      • Introduction
      • Three Features Are Unique to M Phase: Chromosome Condensation, the Mitotic Spindle, and the Contractile Ring
      • Cell Division Depends on the Duplication of the Centrosome
      • M Phase Is Traditionally Divided into Six Stages
      • Large Cytoplasmic Organelles Are Fragmented During M Phase to Ensure That They Are Faithfully Inherited
      • Summary
    • Mitosis
      • Introduction
      • Formation of the Mitotic Spindle in an M-Phase Cell Is Accompanied by Striking Changes in the Dynamic Properties of Microtubules
      • Interactions Between Oppositely Oriented Microtubules Drive Spindle Assembly
      • Replicated Chromosomes Attach to Microtubules by Their Kinetochores
      • Kinetochore Protein Complexes Assemble on Specific Centromeric DNA Sequences in Yeast Chromosomes
      • Kinetochores Capture Microtubules Nucleated by the Spindle Poles
      • The Plus Ends of Kinetochore Microtubules Can Add and Lose Tubulin Subunits While Attached to the Kinetochore
      • Spindle Poles Repel Chromosomes
      • Sister Chromatids Attach by Their Kinetochores to Opposite Spindle Poles
      • Balanced Bipolar Forces Hold Chromosomes on the Metaphase Plate
      • Microtubules Are Dynamic in the Metaphase Spindle
      • Sister Chromatids Separate Suddenly at Anaphase
      • Anaphase Is Delayed Until All Chromosomes Are Positioned at the Metaphase Plate
      • Two Distinct Processes Separate Sister Chromatids at Anaphase
      • Kinetochore Microtubules Disassemble During Anaphase A
      • Two Separate Forces May Contribute to Anaphase B
      • At Telophase the Nuclear Envelope Initially Re-forms Around Individual Chromosomes
      • Summary
    • Cytokinesis
      • Introduction
      • The Mitotic Spindle Determines the Site of Cytoplasmic Cleavage During Cytokinesis
      • The Spindle Is Specifically Repositioned to Create Asymmetric Cell Divisions
      • Actin and Myosin Generate the Forces for Cleavage
      • In Special Cases, Selected Cell Components Can Be Segregated to One Daughter Cell Only
      • Cytokinesis Occurs by a Special Mechanism in Higher Plant Cells
      • A Cytoskeletal Framework Determines the Plane of Plant Cell Division
      • The Elaborate M Phase of Higher Organisms Evolved Gradually from Procaryotic Fission Mechanisms
      • Summary
    • References
      • General
      • Cited
• Part IV. Cells in Their Social Context
  • Chapter 19. Cell Junctions, Cell Adhesion, and the Extracellular Matrix
    • Introduction
    • Cell Junctions
      • Introduction
      • Tight Junctions Form a Selective Permeability Barrier Across Epithelial Cell Sheets
      • Anchoring Junctions Connect the Cytoskeleton of a Cell to Those of Its Neighbors or to the Extracellular Matrix
      • Adherens Junctions Connect Bundles of Actin Filaments from Cell to Cell or from Cell to Extracellular Matrix
      • Desmosomes Connect Intermediate Filaments from Cell to Cell; Hemidesmosomes Connect Them to the Basal Lamina
      • Gap Junctions Allow Small Molecules to Pass Directly from Cell to Cell
      • Gap-Junction Connexons Are Composed of Six Subunits
      • Most Cells in Early Embryos Are Coupled by Gap Junctions
      • The Permeability of Gap Junctions Is Regulated
      • In Plants, Plasmodesmata Perform Many of the Same Functions as Gap Junctions
      • Summary
    • Cell-Cell Adhesion
      • Introduction
      • There Are Two Basic Ways in Which Animal Cells Assemble into Tissues
      • Dissociated Vertebrate Cells Can Reassemble into Organized Tissues Through Selective Cell-Cell Adhesion
      • The Cadherins Mediate Ca²⁺-dependent Cell-Cell Adhesion in Vertebrates
      • Cadherins Mediate Cell-Cell Adhesion by a Homophilic Mechanism
      • Ca²⁺-independent Cell-Cell Adhesion Is Mediated Mainly by Members of the Immunoglobulin Superfamily of Proteins
      • Multiple Types of Cell-Surface Molecules Act in Parallel to Mediate Selective Cell-Cell and Cell-Matrix Adhesion
      • Nonjunctional Contacts May Initiate Tissue-specific Cell-Cell Adhesions That Junctional Contacts Then Orient and Stabilize
      • Summary
    • The Extracellular Matrix of Animals
      • Introduction
      • The Extracellular Matrix Is Made and Oriented by the Cells Within It
      • Glycosaminoglycan (GAG) Chains Occupy Large Amounts of Space and Form Hydrated Gels
      • Hyaluronan Is Thought to Facilitate Cell Migration During Tissue Morphogenesis and Repair
      • Proteoglycans Are Composed of GAG Chains Covalently Linked to a Core Protein
      • Proteoglycans Can Regulate the Activities of Secreted Signaling Molecules
      • GAG Chains May Be Highly Organized in the Extracellular Matrix
      • Cell-Surface Proteoglycans Act as Co-Receptors
      • Collagens Are the Major Proteins of the Extracellular Matrix
      • Collagens Are Secreted with a Nonhelical Extension at Each End
      • After Secretion Fibrillar Procollagen Molecules Are Cleaved to Collagen Molecules, Which Assemble into Fibrils
      • Fibril-associated Collagens Help Organize the Fibrils
      • Cells Help Organize the Collagen Fibrils They Secrete by Exerting Tension on the Matrix
      • Elastin Gives Tissues Their Elasticity
      • Fibronectin Is an Extracellular Adhesive Protein That Helps Cells Attach to the Matrix
      • Multiple Forms of Fibronectin Are Produced by Alternative RNA Splicing
      • Glycoproteins in the Matrix Help Define Cell Migration Pathways
      • Type IV Collagen Molecules Assemble into a Sheetlike Meshwork to Help Form Basal Laminae
      • Basal Laminae Are Composed Mainly of Type IV Collagen, Heparan Sulfate Proteoglycan, Laminin, and Entactin
      • Basal Laminae Perform Diverse and Complex Functions
      • The Degradation of Extracellular Matrix Components Is Tightly Controlled
      • Summary
    • Extracellular Matrix Receptors on Animal Cells: The Integrins
      • Introduction
      • Integrins Are Transmembrane Heterodimers
      • Integrins Must Interact with the Cytoskeleton in Order to Bind Cells to the Extracellular Matrix
      • Integrins Enable the Cytoskeleton and Extracellular Matrix to Communicate Across the Plasma Membrane
      • Cells Can Regulate the Activity of Their Integrins
      • Integrins Can Activate Intracellular Signaling Cascades
      • Summary
    • The Plant Cell Wall
      • Introduction
      • The Composition of the Cell Wall Depends on the Cell Type
      • The Tensile Strength of the Cell Wall Allows Plant Cells to Develop Turgor Pressure
      • The Cell Wall Is Built from Cellulose Microfibrils Interwoven with a Network of Polysaccharides and Proteins
      • Microtubules Orient Cell-Wall Deposition
      • Summary
    • References
      • Cited
  • Chapter 20. Germ Cells and Fertilization
    • Introduction
    • The Benefits of Sex
      • Introduction
      • In Multicellular Animals the Diploid Phase Is Complex and Long, the Haploid Simple and Fleeting
      • Sexual Reproduction Gives a Competitive Advantage to Organisms in an Unpredictably Variable Environment
      • Summary
    • Meiosis
      • Introduction
      • Meiosis Involves Two Nuclear Divisions Rather Than One
      • Genetic Reassortment Is Enhanced by Crossing-over Between Homologous Nonsister Chromatids
      • Meiotic Chromosome Pairing Culminates in the Formation of the Synaptonemal Complex
      • Recombination Nodules Are Thought to Mediate Chromatid Exchanges
      • Chiasmata Play an Important Part in Chromosome Segregation in Meiosis
      • Pairing of the Sex Chromosomes Ensures That They Also Segregate
      • Meiotic Division II Resembles a Normal Mitosis
      • Summary
    • Eggs
      • Introduction
      • An Egg Is the Only Cell in a Higher Animal That Is Able to Develop into a New Individual
      • An Egg Is Highly Specialized for Independent Development, with Large Nutrient Reserves and an Elaborate Coat
      • Eggs Develop in Stages
      • Oocytes Grow to Their Large Size Through Special Mechanisms
      • Summary
    • Sperm
      • Introduction
      • Sperm Are Highly Adapted for Delivering Their DNA to an Egg
      • Sperm Are Produced Continuously in Many Mammals
      • Summary
    • Fertilization
      • Introduction
      • Binding to the Zona Pellucida Induces the Sperm to Undergo an Acrosomal Reaction
      • The Egg Cortical Reaction Helps to Ensure That Only One Sperm Fertilizes the Egg
      • A Transmembrane Fusion Protein in the Sperm Plasma Membrane Catalyzes Sperm-Egg Fusion
      • The Sperm Provides a Centriole for the Zygote
      • Summary
    • References
      • General
      • Cited
  • Chapter 21. Cellular Mechanisms of Development
    • Introduction
    • Morphogenetic Movements and the Shaping of the Body Plan
      • Introduction
      • The Polarity of the Amphibian Embryo Depends on the Polarity of the Egg
      • Cleavage Produces Many Cells from One
      • The Blastula Consists of an Epithelium Surrounding a Cavity
      • Gastrulation Transforms a Hollow Ball of Cells into a Three-layered Structure with a Primitive Gut
      • Gastrulation Movements Are Organized Around the Dorsal Lip of the Blastopore
      • Active Changes of Cell Packing Provide a Driving Force for Gastrulation
      • The Three Germ Layers Formed by Gastrulation Have Different Fates
      • The Mesoderm on Either Side of the Body Axis Breaks Up into Somites from Which Muscle Cells Derive
      • Changing Patterns of Cell Adhesion Molecules Regulate Morphogenetic Movements
      • Embryonic Tissues Are Invaded in a Strictly Controlled Fashion by Migratory Cells
      • The Vertebrate Body Plan Is First Formed in Miniature and Then Maintained as the Embryo Grows
      • Summary
    • Cell Diversification in the Early Animal Embryo
      • Introduction
      • Initial Differences Among Xenopus Blastomeres Arise from the Spatial Segregation of Determinants in the Egg
      • Inductive Interactions Generate New Types of Cells in a Progressively More Detailed Pattern
      • A Simple Morphogen Gradient Can Organize a Complex Pattern of Cell Responses
      • Cells Can React Differently to a Signal According to the Time When They Receive It: The Role of an Intracellular Clock
      • In Mammals the Protected Uterine Environment Permits an Unusual Style of Early Development
      • All the Cells of the Very Early Mammalian Embryo Have the Same Developmental Potential
      • Mammalian Embryonic Stem Cells Show How Environmental Cues Can Control the Pace as well as the Pathway of Development
      • Summary
    • Cell Memory, Cell Determination, and the Concept of Positional Values
      • Introduction
      • Cells Often Become Determined for a Future Specialized Role Long Before They Differentiate Overtly
      • The Time of Cell Determination Can Be Discovered by Transplantation Experiments
      • Cell Determination and Differentiation Reflect the Expression of Regulatory Genes
      • The State of Determination May Be Governed by the Cytoplasm or Be Intrinsic to the Chromosomes
      • Cells in Developing Tissues Remember Their Positional Values
      • The Pattern of Positional Values Controls Cell Proliferation and Is Regulated by Intercalation
      • Summary
    • The Nematode Worm: Developmental Control Genes and the Rules of Cell Behavior
      • Introduction
      • Caenorhabditis elegans Is Anatomically and Genetically Simple
      • Nematode Development Is Almost Perfectly Invariant
      • Developmental Control Genes Define the Rules of Cell Behavior That Generate the Body Plan
      • Induction of the Vulva Depends on a Large Set of Developmental Control Genes
      • Genetic and Microsurgical Tests Reveal the Logic of Developmental Control; Gene Cloning and Sequencing Help to Reveal Its Biochemistry
      • Heterochronic Mutations Identify Genes That Specify Changes in the Rules of Cell Behavior as Time Goes By
      • The Tempo of Development Is Not Controlled by the Cell-Division Cycle
      • Cells Die Tidily as a Part of the Program of Development
      • Summary
    • Drosophila and the Molecular Genetics of Pattern Formation. I. Genesis of the Body Plan
      • Introduction
      • The Insect Body Is Constructed by Modulation of a Fundamental Pattern of Repeating Units
      • Drosophila Begins Its Development as a Syncytium
      • Two Orthogonal Systems Define the Ground Plan of the Embryo
      • The Patterning of the Embryo Begins with Influences from the Cells Surrounding the Egg
      • The Dorsoventral Axis Is Specified Inside the Embryo by a Gene Regulatory Protein with a Graded Intranuclear Concentration
      • The Posterior System Specifies Germ Cells as well as Posterior Body Segments
      • mRNA Localized at the Anterior Pole Codes for a Gene Regulatory Protein That Forms an Anterior Morphogen Gradient
      • Three Classes of Segmentation Genes Subdivide the Embryo
      • The Localized Expression of Segmentation Genes Is Regulated by a Hierarchy of Positional Signals
      • The Product of One Segmentation Gene Controls the Expression of Another to Create a Detailed Pattern
      • Egg-Polarity, Gap, and Pair-Rule Genes Create a Transient Pattern That Is Remembered by Other Genes
      • Segment-Polarity Genes Label the Basic Subdivisions of Every Parasegment
      • Summary
    • Drosophila and the Molecular Genetics of Pattern Formation. II. Homeotic Selector Genes and the Patterning of Body Parts
      • Introduction
      • The Homeotic Selector Genes of the Bithorax Complex and the Antennapedia Complex Specify the Differences Among Parasegments
      • Homeotic Selector Genes Encode a System of Molecular Address Labels
      • The Control Regions of the Homeotic Selector Genes Act as Memory Chips for Positional Information
      • The Adult Fly Develops from a Set of Imaginal Discs That Carry Remembered Positional Information
      • Homeotic Selector Genes Are Essential for the Memory of Positional Information in Imaginal Disc Cells
      • The Homeotic Selector Genes and Segment-Polarity Genes Define Compartments of the Body
      • Localized Expression of Specific Gene Regulatory Proteins Foreshadows the Production of Sensory Bristles
      • Lateral Inhibition Regulates the Fine-grained Pattern of Differentiated Cell Types
      • The Developmental Control Genes of Drosophila Have Homologues in Vertebrates
      • Mammals Have Four Homologous HOM Complexes
      • Hox Genes Specify Positional Values in Vertebrates as in Insects
      • Subsets of Hox Genes Are Expressed in Order Along Two Orthogonal Axes in the Vertebrate Limb Bud
      • Summary
    • Plant Development
      • Introduction
      • Embryonic Development Starts by Establishing a Root-Shoot Axis and Then Halts Inside the Seed
      • The Repetitive Modules of a Plant Are Generated Sequentially by Meristems
      • The Shaping of Each New Structure Depends on Oriented Cell Division and Expansion
      • Each Plant Module Grows from a Microscopic Set of Primordia in a Meristem
      • Long-range Hormonal Signals Coordinate Developmental Events in Separate Parts of the Plant
      • Arabidopsis Serves as a Model Organism for Plant Molecular Genetics
      • Homeotic Selector Genes Specify the Parts of a Flower
      • Summary
    • Neural Development
      • Introduction
      • Stocks of Neurons Are Generated at the Outset of Neural Development and Are Not Subsequently Replenished
      • The Time and Place of a Neuron's Birth Determine the Connections It Will Form
      • Each Axon or Dendrite Extends by Means of a Growth Cone at Its Tip
      • The Growth Cone Pilots the Developing Neurite Along a Precisely Defined Path in Vivo
      • Target Tissues Release Neurotrophic Factors That Control Nerve Cell Growth and Survival
      • The Positional Values of Neurons Guide the Formation of Orderly Neural Maps: The Doctrine of Neuronal Specificity
      • Axons from Opposite Sides of the Retina Respond Differently to a Gradient of Repulsive Molecules in the Tectum
      • Diffuse Patterns of Synaptic Connections Are Sharpened by Activity-dependent Synapse Elimination
      • Experience Molds the Pattern of Synaptic Connections in the Brain
      • Summary
    • References
      • General
      • Cited
  • Chapter 22. Differentiated Cells and the Maintenance of Tissues
    • Introduction
    • Maintenance of the Differentiated State
      • Introduction
      • Most Differentiated Cells Remember Their Essential Character Even in a Novel Environment
      • The Differentiated State Can Be Modulated by a Cell's Environment
      • Summary
    • Tissues with Permanent Cells
      • Introduction
      • The Cells at the Center of the Lens of the Adult Eye Are Remnants of the Embryo
      • Most Permanent Cells Renew Their Parts: The Photoreceptor Cells of the Retina
      • Summary
    • Renewal by Simple Duplication
      • Introduction
      • The Liver Functions as an Interface Between the Digestive Tract and the Blood
      • Liver Cell Loss Stimulates Liver Cell Proliferation
      • Regeneration Requires Coordinated Growth of Tissue Components
      • Endothelial Cells Line All Blood Vessels
      • New Endothelial Cells Are Generated by Simple Duplication of Existing Endothelial Cells
      • New Capillaries Form by Sprouting
      • Angiogenesis Is Controlled by Growth Factors Released by the Surrounding Tissues
      • Summary
    • Renewal by Stem Cells: Epidermis
      • Introduction
      • Stem Cells Can Divide Without Limit and Give Rise to Differentiated Progeny
      • Epidermal Stem Cells Lie in the Basal Layer
      • Differentiating Epidermal Cells Synthesize a Sequence of Different Keratins as They Mature
      • Epidermal Stem Cells Are a Subset of Basal Cells
      • Basal Cell Proliferation Is Regulated According to the Thickness of the Epidermis
      • Secretory Cells in the Epidermis Are Secluded in Glands That Have Their Own Population Kinetics
      • Summary
    • Renewal by Pluripotent Stem Cells: Blood Cell Formation
      • Introduction
      • There Are Three Main Categories of White Blood Cells: Granulocytes, Monocytes, and Lymphocytes
      • The Production of Each Type of Blood Cell in the Bone Marrow Is Individually Controlled
      • Bone Marrow Contains Hemopoietic Stem Cells
      • A Pluripotent Stem Cell Gives Rise to All Classes of Blood Cells
      • The Number of Specialized Blood Cells Is Amplified by Divisions of Committed Progenitor Cells
      • The Factors That Regulate Hemopoiesis Can Be Analyzed in Culture
      • Erythropoiesis Depends on the Hormone Erythropoietin
      • Multiple CSFs Influence the Production of Neutrophils and Macrophages
      • Hemopoietic Stem Cells Depend on Contact with Cells Expressing the Steel Factor
      • The Behavior of a Hemopoietic Cell Depends Partly on Chance
      • Regulation of Cell Survival Is as Important as Regulation of Cell Proliferation
      • Summary
    • Genesis, Modulation, and Regeneration of Skeletal Muscle
      • Introduction
      • New Skeletal Muscle Cells Form by the Fusion of Myoblasts
      • Muscle Cells Can Vary Their Properties by Changing the Protein Isoforms That They Contain
      • Some Myoblasts Persist as Quiescent Stem Cells in the Adult
      • Summary
    • Fibroblasts and Their Transformations: The Connective-Tissue Cell Family
      • Introduction
      • Fibroblasts Change Their Character in Response to Signals in the Extracellular Matrix
      • The Extracellular Matrix May Influence Connective-Tissue Cell Differentiation by Affecting Cell Shape and Attachment
      • Different Signaling Molecules Act Sequentially to Regulate Production of Fat Cells
      • Bone Is Continually Remodeled by the Cells Within It
      • Osteoblasts Secrete Bone Matrix, While Osteoclasts Erode It
      • During Development, Cartilage Is Eroded by Osteoclasts to Make Way for Bone
      • The Structure of the Body Is Stabilized by Its Connective-Tissue Framework and by the Selective Cohesion of Cells
      • Summary
    • Appendix
      • Cells of the Adult Human Body: A Catalogue
    • References
      • General
      • Cited
  • Chapter 23. The Immune System
    • Introduction
    • The Cellular Basis of Immunity
      • Introduction
      • B Lymphocytes Make Humoral Antibody Responses; T Lymphocytes Make Cell-mediated Immune Responses
      • Lymphocytes Develop in Primary Lymphoid Organs and React with Foreign Antigens in Secondary Lymphoid Organs
      • Cell-Surface Markers Make It Possible to Distinguish and Separate T and B Cells
      • The Immune System Works by Clonal Selection
      • Most Antigens Stimulate Many Different Lymphocyte Clones
      • Most Lymphocytes Continuously Recirculate
      • Immunological Memory Is Due to Clonal Expansion and Lymphocyte Maturation
      • The Failure to Respond to Self Antigens Is Due to Acquired Immunological Tolerance
      • Summary
    • The Functional Properties of Antibodies
      • Introduction
      • The Antigen-specific Receptors on B Cells Are Antibody Molecules
      • B Cells Can Be Stimulated to Secrete Antibodies in a Culture Dish
      • Antibodies Have Two Identical Antigen-binding Sites
      • An Antibody Molecule Is Composed of Two Identical Light Chains and Two Identical Heavy Chains
      • There Are Five Classes of Heavy Chains, Each with Different Biological Properties
      • Antibodies Can Have Either k or l Light Chains, but Not Both
      • The Strength of an Antibody-Antigen Interaction Depends on Both the Number of Antigen-binding Sites Occupied and the Affinity of Each Binding Site
      • Antibodies Recruit Complement to Help Fight Bacterial Infections
      • Summary
    • The Fine Structure of Antibodies
      • Introduction
      • Light and Heavy Chains Consist of Constant and Variable Regions
      • The Light and Heavy Chains Each Contain Three Hypervariable Regions That Together Form the Antigen-binding Site
      • The Light and Heavy Chains Are Folded into Repeating Similar Domains
      • X-ray Diffraction Studies Have Revealed the Structure of Ig Domains and Antigen-binding Sites in Three Dimensions
      • Summary
    • The Generation of Antibody Diversity
      • Introduction
      • Antibody Genes Are Assembled from Separate Gene Segments During B Cell Development
      • Each V Region Is Encoded by More Than One Gene Segment
      • Imprecise Joining of Gene Segments Greatly Increases the Diversity of V Regions
      • Antigen-driven Somatic Hypermutation Fine-tunes Antibody Responses
      • Antibody Gene-Segment Joining Is Regulated to Ensure That B Cells Are Monospecific
      • When Stimulated by Antigen, B Cells Switch from Making a Membrane-bound Antibody to Making a Secreted Form of the Same Antibody
      • B Cells Can Switch the Class of Antibody They Make
      • Summary
    • T Cell Receptors and Subclasses
      • Introduction
      • T Cell Receptors Are Antibodylike Heterodimers
      • Different T Cell Responses Are Mediated by Distinct Classes of T Cells
      • Summary
    • MHC Molecules and Antigen Presentation to T Cells
      • Introduction
      • There Are Two Principal Classes of MHC Molecules
      • X-ray Diffraction Studies Reveal the Antigen-binding Site of MHC Proteins as well as the Bound Peptide
      • Class I and Class II MHC Molecules Have Different Functions
      • CD4 and CD8 Proteins Act as MHC-binding Co-Receptors on Helper and Cytotoxic T Cells, Respectively
      • Summary
    • Cytotoxic T Cells
      • Introduction
      • Cytotoxic T Cells Recognize Fragments of Viral Proteins on the Surface of Virus-infected Cells
      • MHC-encoded ABC Transporters Transfer Peptide Fragments from the Cytosol to the ER Lumen
      • Cytotoxic T Cells Induce Infected Target Cells to Kill Themselves
      • Summary
    • Helper T Cells and T Cell Activation
      • Introduction
      • Helper T Cells Recognize Fragments of Endocytosed Foreign Protein Antigens in Association with Class II MHC Proteins
      • Helper T Cells Are Activated by Antigen-presenting Cells
      • The T Cell Receptor Forms Part of a Large Signaling Complex in the Plasma Membrane
      • Two Simultaneous Signals Are Required for Helper T Cell Activation
      • Helper T Cells, Once Activated, Stimulate Themselves and Other T Cells to Proliferate by Secreting Interleukin-2
      • Helper T Cells Are Required for Most B Cells to Respond to Antigen
      • The Activation of B Cells by Helper T Cells Is Mediated by Both Membrane-bound and Secreted Signals
      • Some Helper T Cells Help Activate Cytotoxic T Cells and Macrophages by Secreting Interleukins
      • Summary
    • Selection of the T Cell Repertoire
      • Introduction
      • Developing T Cells That Recognize Peptides in Association with Self MHC Molecules Are Positively Selected in the Thymus
      • Developing T Cells That React Strongly with Self Peptides Bound to Self MHC Molecules Are Eliminated in the Thymus
      • Some Allelic Forms of MHC Molecules Are Ineffective at Presenting Specific Antigens to T Cells: Immune Response ( Ir ) Genes
      • The Role of MHC Proteins in Antigen Presentation to T Cells Provides an Explanation for Transplantation Reactions and MHC Polymorphism
      • Immune Recognition Molecules Belong to an Ancient Superfamily
      • Summary
    • References
      • General
      • Cited
  • Chapter 24. Cancer
    • Introduction
    • Cancer as a Microevolutionary Process
      • Introduction
      • Cancers Differ According to the Cell Type from Which They Derive
      • Most Cancers Derive from a Single Abnormal Cell
      • Most Cancers Are Probably Initiated by a Change in the Cell's DNA Sequence
      • A Single Mutation Is Not Enough to Cause Cancer
      • Cancers Develop in Slow Stages from Mildly Aberrant Cells
      • Tumor Progression Involves Successive Rounds of Mutation and Natural Selection
      • The Development of a Cancer Can Be Promoted by Factors That Do Not Alter the Cell's DNA Sequence
      • Most Cancers Result from Avoidable Combinations of Environmental Causes
      • The Search for Cancer Cures Is Hard but Not Hopeless
      • Cancerous Growth Often Depends on Deranged Control of Cell Differentiation or Cell Death
      • To Metastasize, Cancer Cells Must Be Able to Cross Basal Laminae
      • Mutations That Increase the Mutation Rate Accelerate the Development of Cancer
      • The Enhanced Mutability of Cancer Cells Helps Them Evade Destruction by Anticancer Drugs
      • Summary
    • The Molecular Genetics of Cancer
      • Introduction
      • Retroviruses Can Act as Vectors for Oncogenes That Transform Cell Behavior
      • Retroviruses Pick Up Oncogenes by Accident
      • A Retrovirus Can Transform a Host Cell by Inserting Its DNA Next to a Proto-oncogene of the Host
      • Different Searches for the Genetic Basis of Cancer Converge on Disturbances in the Same Proto-oncogenes
      • A Proto-oncogene Can Be Made Oncogenic in Many Ways
      • The Actions of Oncogenes Can Be Assayed Singly and in Combination in Transgenic Mice
      • Loss of One Copy of a Tumor Suppressor Gene Can Create a Hereditary Predisposition to Cancer
      • Loss of the Retinoblastoma Tumor Suppressor Gene Plays a Part in Many Different Cancers
      • DNA Tumor Viruses Activate the Cell's DNA Replication Machinery as Part of Their Strategy for Survival
      • DNA Tumor Viruses Activate the Cell's Replication Machinery by Blocking the Action of Key Tumor Suppressor Genes
      • Mutations of the p53 Gene Disable an Emergency Brake on Cell Proliferation and Lead to Genetic Instability
      • Colorectal Cancers Develop Slowly Via a Succession of Visible Structural Changes
      • Mutations Leading to Colorectal Cancer Can Be Identified by Scanning the Cancer Cells and by Studying Families Prone to the Cancer
      • Genetic Deletions in Colorectal Cancer Cells Reveal Sites of Loss of Tumor Suppressor Genes
      • The Steps of Tumor Progression Can Be Correlated with Specific Mutations
      • Each Case of Cancer Is Characterized by Its Own Array of Genetic Lesions
      • Summary
    • References
      • General
      • Cited

Bruce Alberts received his PhD from Harvard University and is currently President of the National Academy of Sciences and Professor of Biochemistry and Biophysics at the University of California, San Francisco. Dennis Bray received his PhD from the Massachusetts Institute of Technology and is currently a Medical Research Council Fellow in the Department of Zoology, University of Cambridge. Julian Lewis received his DPhil from the University of Oxford and is currently a Senior Scientist in the Imperial Cancer Research Fund Development Biology Unit, University of Oxford. Martin Raff received his MD from McGill University and is currently a Professor in the MRC Laboratory for Molecular Cell Biology and the Biology Department, University College London. Keith Roberts received his PhD from the University of Cambridge and is currently Head of the Department of Cell Biology, the John Innes Institute, Norwich. James D Watson received his PhD from Indiana University and is currently Director of Cold Spring Harbor Laboratory. He is the author of Molecular Biology of the Gene and, with Francis Crick and Maurice Wilkins, won the Nobel Peace Prize in Medicine and Physiology in 1962.