Antagonism between G(o)α and G(q)α in Caenorhabditis elegans: The RGS protein EAT-16 is necessary for G(o)α signaling and regulates G(q)α activity

Abstract

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)α) 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)α and negatively regulate EGL-30 (Gq(α)) 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)/G11 in COS-7 cells. Animals defective in both sag-1 and eat-16 are inviable, but reducing function in egl-30 restores viability, indicating that the lethality of the eat-16; sag-1 double mutant is due to excessive G(q)α activity. Analysis of these mutations indicates that the G(o) and G(q) pathways function antagonistically in C. elegans, and that G(o)α negatively regulates the G(q) pathway, possibly via EAT-16 or SAG-1. We propose that a major cellular role of Go is to antagonize signaling by G(q).