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

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.