Antagonism between Goα and Gqα in Caenorhabditis elegans:: the RGS protein EAT-16 is necessary for Goα signaling and regulates Gqα activity

被引:141
作者
Hajdu-Cronin, YM
Chen, WJ
Patikoglou, G
Koelle, MR
Sternberg, PW [1 ]
机构
[1] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA
[2] CALTECH, Div Biol, Pasadena, CA 91125 USA
[3] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA
关键词
C; elegans; G(o) protein; G(q) protein; RGS protein; signaling; regulation;
D O I
10.1101/gad.13.14.1780
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
To elucidate the cellular role of the heterotrimeric G protein G(o), we have taken a molecular genetic approach in Caenorhabditis elegans. We screened for suppressors of activated GOA-1 (G(o)alpha) that do not simply decrease its expression and found mutations in only two genes, sag-1 and eat-16. Animals defective in either gene display a hyperactive phenotype similar to that of goa-1 loss-of-function mutants. Double-mutant analysis indicates that both sag-1 and eat-16 act downstream of, or parallel to, G(o)alpha and negatively regulate EGL-30 (G(q)alpha) signaling. eat-16 encodes a regulator of G protein signaling (RGS) most similar to the mammalian RGS7 and RGS9 proteins and can inhibit endogenous mammalian G(q)/G(11) in COS-7 cells. Animals defective in both sag-1 and eat-16 are inviable, but reducing function in eg1-30 restores viability, indicating that the lethality of the eat-16; sag-1 double mutant is due to excessive G(q)alpha activity. Analysis of these mutations indicates that the G(o) and G(q) pathways function antagonistically in C. elegans, and that G(o)alpha. negatively regulates the G(q) pathway, possibly via EAT-16 or SAG-1. We propose that a major cellular role of G(o) is to antagonize signaling by G(q).
引用
收藏
页码:1780 / 1793
页数:14
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