Gβγ Signaling: Lessons Across the Cellular Multiverse

The eponymous term Gβγ protein has given way to a more nuanced view of 60 different possible combinations of the 5 Gβ and 12 Gγ subunits and their effects on cellular signaling profiles. Beyond this increased appreciation of their diversity per se, we now know that distinct Gβγ combinations may play roles beyond the regulation of cell surface effectors following G protein–coupled receptor activation and release from G protein heterotrimers. Gβγ subunits operate in multiple subcellular compartments. In this review, we focus on Gβγ-mediated events in the endoplasmic reticulum, Golgi apparatus, and mitochondria and particularly highlight Gβγ roles in the nucleus.