The heel and toe of the cell's foot: a multifaceted approach for understanding the structure and dynamics of focal adhesions

Cell Motil Cytoskeleton. 2009 Nov;66(11):1017-29. doi: 10.1002/cm.20410.

Abstract

Focal adhesions (FAs) are large clusters of transmembrane receptors of the integrin family and a multitude of associated cytoplasmic "plaque" proteins, which connect the extracellular matrix-bound receptors with the actin cytoskeleton. The formation of nearly stationary FAs defines a boundary between the dense and highly dynamic actin network in lamellipodium and the sparser and more diverse cytoskeletal organization in the lamella proper, creating a template for the organization of the entire actin network. The major "mechanical" and "sensory" functions of FAs; namely, the nucleation and regulation of the contractile, myosin-II-containing stress fibers and the mechanosensing of external surfaces depend, to a major extent, on the dynamics of molecular components within FAs. A central element in FA regulation concerns the positive feedback loop, based on the most intriguing feature of FAs; that is, their dependence on mechanical tension developing by the growing stress fibers. FAs grow in response to such tension, and rapidly disassemble upon its relaxation. In this article, we address the mechanistic relationships between the process of FA development, maturation and dissociation and the dynamic molecular events, which take place in different regions of the FA, primarily in the distal end of this structure (the "toe") and the proximal "heel," and discuss the central role of local mechanical forces in orchestrating the complex interplay between FAs and the actin system.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Adhesion Molecules / metabolism
  • Cell Adhesion Molecules / ultrastructure
  • Cell Movement*
  • Cytoskeletal Proteins / chemistry
  • Cytoskeletal Proteins / metabolism
  • Cytoskeletal Proteins / ultrastructure*
  • Extracellular Matrix Proteins / chemistry
  • Extracellular Matrix Proteins / metabolism
  • Extracellular Matrix Proteins / ultrastructure
  • Focal Adhesions / chemistry
  • Focal Adhesions / metabolism*
  • Focal Adhesions / ultrastructure
  • Humans
  • Pseudopodia / chemistry
  • Pseudopodia / metabolism*
  • Pseudopodia / ultrastructure
  • Stress, Mechanical

Substances

  • Cell Adhesion Molecules
  • Cytoskeletal Proteins
  • Extracellular Matrix Proteins