Membrane-tethered ligands: tools for cell-autonomous pharmacological manipulation of biological circuits

Physiology (Bethesda). 2013 May;28(3):164-71. doi: 10.1152/physiol.00056.2012.

Abstract

Detection of secreted signaling molecules by cognate cell surface receptors is a major intercellular communication pathway in cellular circuits that control biological processes. Understanding the biological significance of these connections would allow us to understand how cellular circuits operate as a whole. Membrane-tethered ligands are recombinant transgenes with structural modules that allow them to act on cell-surface receptors and ion channel subtypes with pharmacological specificity in a cell-autonomous manner. Membrane-tethered ligands have been successful in the specific manipulation of ion channels as well as G-protein-coupled receptors, and, in combination with cell-specific promoters, such manipulations have been restricted to genetically defined subpopulations within cellular circuits in vivo to induce specific phenotypes controlled by those circuits. These studies establish the membrane-tethering approach as a generally applicable method for dissecting neural and physiological circuits.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Humans
  • Ion Channels / metabolism*
  • Ligands
  • Neurotoxins / genetics
  • Neurotoxins / metabolism
  • Protein Binding
  • Receptors, Cell Surface / metabolism*
  • Receptors, Nicotinic / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*
  • Signal Transduction*
  • Transgenes

Substances

  • Adaptor Proteins, Signal Transducing
  • GPI-Linked Proteins
  • Ion Channels
  • LYNX1 protein, human
  • Ligands
  • Neurotoxins
  • Receptors, Cell Surface
  • Receptors, Nicotinic
  • Recombinant Fusion Proteins