Specificity of Receptor–G Protein Coupling: Protein Structure and Cellular Determinants

G protein-coupled receptors are involved in a tremendous range of signaling processes in the nervous system. The outlines of a molecular basis for specificity of receptor–G protein coupling has been established, but important details remain unclear. The second and third intracellular loops of most G protein-coupled receptors and the carboxyl terminus of the G protein α subunit have the most clearly established roles in specificity of coupling. The role of other regions of receptor and G protein, especially the Gβγ subunit, is an area needing more investigation. A discrepancy between specificity observedin vitroand in intact cells suggests a role for targeting and compartmentation of signaling components to account for the striking specificity observed in intact cells. The role of caveolin and PDZ domain-containing proteins will be of significant interest.