Diversity of the Gβγ complexes defines spatial and temporal bias of GPCR signaling

The signal transduction by G-protein-coupled receptors (GPCRs) is mediated by heterotrimeric G proteins composed from one of the 16 G alpha subunits and the inseparable G beta gamma complex assembled from a repertoire of 5 G beta and 12 G gamma subunits. However, the functional role of compositional diversity in G beta gamma complexes has been elusive. Using optical biosensors, we examined the function of all G beta gamma combinations in living cells and uncovered two major roles of G beta gamma diversity. First, we demonstrate that the identity of G beta gamma subunits greatly influences the kinetics and efficacy of GPCR responses at the plasma membrane. Second, we show that different G beta gamma combinations are selectively dispatched from the plasma membrane to various cellular organelles on a timescale from milliseconds to minutes. We describe the mechanisms regulating these processes and document their implications for GPCR signaling via various G alpha subunits, thereby illustrating a role for the compositional diversity of G protein heterotrimers.

Automated summary

The compositional diversity of G beta gamma complexes plays a crucial role in modulating GPCR signaling, influencing the kinetics and efficacy of GPCR responses at the plasma membrane, as well as selectively dispatching different G beta gamma combinations to various cellular organelles.