Co-expression of Gbeta5 enhances the function of two Ggamma subunit-like domain-containing regulators of G protein signaling proteins.
Regulators of G protein signaling (RGS) stimulate the GTPase activity of G protein Galpha subunits and probably play additional roles. Some RGS proteins contain a Ggamma subunit-like (GGL) domain, which mediates a specific interaction with Gbeta5. 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 Gbeta5 on RGS function. Co-expression of either RGS7 or RGS9 modestly accelerated GIRK channel kinetics. When Gbeta5 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 Gbeta1, and co-expression of Gbeta5 alone had no effect on GIRK channel kinetics. Gbeta5 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 Gbeta5 was not a consequence of an increase in the amount of plasma membrane or cytosolic RGS7 protein.
Kovoor
A
A
Division of Biology, California Institute of Technology, Pasadena, California 91125, USA.
Chen
C K
CK
He
W
W
Wensel
T G
TG
Simon
M I
MI
Lester
H A
HA
D000818:Animals; D044387:GTP-Binding Protein beta Subunits; D019204:GTP-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D020962:Heterotrimeric GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D015640:Ion Channel Gating; D015221:Potassium Channels / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014981:Xenopus
D044387:GTP-Binding Protein beta Subunits; C094668:Gnb5 protein, mouse; D015221:Potassium Channels; D019204:GTP-Binding Proteins; D020962:Heterotrimeric GTP-Binding Proteins