Subtype-dependent regulation of Gβγ signalling

G protein-coupled receptors (GPCRs) transmit information to the cell interior by transducing external signals to heterotrimeric G protein subunits, G? and G?? subunits, localized on the inner leaflet of the plasma membrane. Though the initial focus was mainly on G?-mediated events, G?? subunits were later identified as major contributors to GPCR-G protein signalling. A broad functional array of G?? signalling has recently been attributed to G? and G? subtype diversity, comprising 5 G? and 12 G? subtypes, respectively. In addition to displaying selectivity towards each other to form the G?? dimer, numerous studies have identified preferences of distinct G?? combinations for specific GPCRs, G? subtypes and effector molecules. Importantly, G? and G? subtypedependent regulation of downstream effectors, representing a diverse range of signalling pathways and physiological functions have been found. Here, we review the literature on the repercussions of G? and G? subtype diversity on direct and indirect regulation of GPCR/G protein signalling events and their physiological outcomes. Our discussion additionally provides perspective in understanding the intricacies underlying molecular regulation of subtype-specific roles of G?? signalling and associated diseases.

Automated summary

G protein-coupled receptors transmit information to the cell interior through the diversity of Gα and Gβ subtypes, affecting downstream effector molecules. Studies have found preferences of distinct Gβγ combinations for specific GPCRs, Gα subtypes, and effector molecules.