Co-expression of Gβ5 enhances the function of two Gγ subunit-like domain-containing regulators of G protein signaling proteins

Regulators of G protein signaling (RGS) stimulate the GTPase activity of G protein G alpha subunits and probably play additional roles. Some RGS proteins contain a G gamma subunit-like (GGL) domain, which mediates a specific interaction with G beta 5, The role of such interactions in RGS function is unclear. RGS proteins can accelerate the kinetics of coupling of G protein-coupled receptors to G-protein-gated inwardly rectifying K+ (GIRK) channels. Therefore, we coupled m2-muscarinic acetylcholine receptors to GIRK channels in Xenopus oocytes to evaluate the effect of G beta 5 on RGS function. Co-expression of either RGS7 or RGS9 modestly accelerated GIRK channel kinetics. When G beta 5 was co-expressed with either RGS7 or RGS9, the acceleration of GIRK channel kinetics was strongly increased over that produced by RGS7 or RGS9 alone. RGS function was not enhanced by co-expression of G beta 1, and co-expression of G beta 5 alone had no effect on GIRK channel kinetics. G beta 5 did not modulate the function either of RGS4, an RGS protein that lacks a GGL domain, or of a functional RGS7 construct in which the GGL domain was omitted. Enhancement of RGS7 function by G beta 5 was not a consequence of an increase in the amount of plasma membrane or cytosolic RGS7 protein.