Co-expression of G beta 5 enhances the function of two G gamma 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 prote ins 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) channel s. Therefore, we coupled m2-muscarinic acetylcholine receptors to GIRK chan nels 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 kin etics. When G beta 5 was co-expressed with either RGS7 or RGS9, the acceler ation 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 be ta 1, and co-expression of G beta 5 alone had no effect on GIRK channel kin etics. G beta 5 did not modulate the function either of RGS4, an RGS protei n that lacks a GGL domain, or of a functional RGS7 construct in which the G GL domain was omitted. Enhancement of RGS7 function by G beta 5 was not a c onsequence of an increase in the amount of plasma membrane or cytosolic RGS 7 protein.