The Role of Gβγ Subunits in the Organization, Assembly, and Function of GPCR Signaling Complexes

The role of G beta gamma subunits in cellular signaling has become well established in the past 20 years. Not only do they regulate effectors once thought to be the sole targets of G alpha subunits, but it has become clear that they also have a unique set of binding partners and regulate signaling pathways that are not always localized to the plasma membrane. However, this may be only the beginning of the story. G beta gamma subunits interact with G protein-coupled receptors, G alpha subunits, and several different effector molecules during assembly and trafficking of receptor-based signaling complexes and not simply in response to ligand stimulation at sites of receptor cellular activity. G beta gamma assembly itself seems to be tightly regulated via the action of molecular chaperones and in turn may serve a similar role ill the assembly of specific signaling complexes. le propose that specific G beta gamma subunits have a broader role in controlling the architecture, assembly, and activity of cellular signaling pathways.