The Expanding Roles of Gβγ Subunits in G Protein-Coupled Receptor Signaling and Drug Action

G beta gamma subunits from heterotrimeric G proteins perform a vast array of functions in cells with respect to signaling, often independently as well as in concert with G alpha subunits. However, the eponymous term G beta gamma does not do justice to the fact that 5 G beta and 12 G gamma isoforms have evolved in mammals to serve much broader roles beyond their canonical roles in cellular signaling. We explore the phylogenetic diversity of G beta gamma subunits with a view toward understanding these expanded roles in different cellular organelles. We suggest that the particular content of distinct G beta gamma subunits regulates cellular activity, and that the granularity of individual G beta and G gamma action is only beginning to be understood. Given the therapeutic potential of targeting G beta gamma action, this larger view serves as a prelude to more specific development of drugs aimed at individual isoforms.