Antagonism between Goalpha and Gqalpha in Caenorhabditis elegans: the RGS protein EAT-16 is necessary for Goalpha signaling and regulates Gqalpha 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 ␣) 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 ␣ and negatively regulate EGL-30 (G q ␣) 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 egl-30 restores viability, indicating that the lethality of the eat-16; sag-1 double mutant is due to excessive G q ␣ activity. Analysis of these mutations indicates that the G o and G q pathways function antagonistically in C. elegans, and that G o ␣ 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 .

Antagonistic sensory cues generate gustatory plasticity in Caenorhabditis elegans

“…Mutation of both the IP 3 receptor ITR-1 (Baylis et al, 1999;Dal Santo et al, 1999) and the DAG kinase DGK-1, essential for reduction of DAG levels (Hadju-Cronin et al, 1999;Nurrish et al, 1999), strongly reduced avoidance after preexposure, but did not affect chemoattraction to 0.1-100 mM NaCl or avoidance of 1 M NaCl ( Figure 6C and D, results not shown). This indicates that IP 3 and DAG signalling are only involved in the plasticity response.…”

Feeding status and serotonin rapidly and reversibly modulate a Caenorhabditis elegans chemosensory circuit

“…In the presence of food (Escherichia coli is used as a food source in the laboratory), pharyngeal pumping (7,8), egg laying (8,9), and male mating (10) are increased, whereas locomotion is decreased (11). Conversely, in the absence of food, the opposite behaviors are observed.…”

G o α regulates olfactory adaptation by antagonizing G q α-DAG signaling in Caenorhabditis elegans

“…Therefore, we tested the participation of these RGS proteins and GPB-2 in adaptation. As a result, two eat-16 alleles, eat-16(ce71) (40) and eat-16(sa609) (24), which are putative null and loss-of-function mutants, respectively, and animals carrying a high-copy array of the egl-10 gene nIs51 (37) showed modest defects in adaptation (Fig. 4C).…”

“…Previous reports have shown that GOA-1 and EGL-30 antagonistically regulate acetylcholine release at neuromuscular junctions (24)(25)(26)(27). Hence, we hypothesized that EGL-30 also has an effect opposite to GOA-1 in adaptation.…”

“…Mutations in goa-1 cause various defects in behaviors, including locomotion and egg laying. The locomotion rate was shown to be antagonistically regulated by GOA-1 G o ␣ and EGL-30 G q ␣ signaling cascades (23)(24)(25)(26)(27). The stimulation of EGL-30 causes a rise of diacylglycerol (DAG) level through activation of EGL-8 PLC␤, leading to a change in distribution of UNC-13, resulting in facilitation of acetylcholine release at neuromuscular junctions (25,26).…”