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

  1. Yvonne M. Hajdu-Cronin,
  2. Wen J. Chen,
  3. Georgia Patikoglou,
  4. Michael R. Koelle, and
  5. Paul W. Sternberg
  1. Howard Hughes Medical Institute (HHMI) and Division of Biology, California Institute of Technology, Pasadena, California 91125 USA; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520 USA

Abstract

To elucidate the cellular role of the heterotrimeric G protein Go, we have taken a molecular genetic approach inCaenorhabditis elegans. We screened for suppressors of activated GOA-1 (Goα) that do not simply decrease its expression and found mutations in only two genes, sag-1 andeat-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 andeat-16 act downstream of, or parallel to, Goα and negatively regulate EGL-30 (Gqα) signaling. eat-16encodes a regulator of G protein signaling (RGS) most similar to the mammalian RGS7 and RGS9 proteins and can inhibit endogenous mammalian Gq/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 Gqα activity. Analysis of these mutations indicates that the Go and Gq pathways function antagonistically in C. elegans, and that Goα negatively regulates the Gq pathway, possibly via EAT-16 or SAG-1. We propose that a major cellular role of Go is to antagonize signaling by Gq.

Keywords

Footnotes

  • These authors contributed equally to this work.

  • Corresponding author.

  • E-MAIL pws{at}cco.caltech.edu; FAX (626) 568-8012.

    • Received April 26, 1999.
    • Accepted June 2, 1999.
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