eat-11 encodes GPB-2, a Gβ5 ortholog that interacts with Goα and Gqα to regulate C. elegans behavior

Genetic analysis indicates that the gene eat-11 is involved locomotion and egg laying [1–8]. Genetic analysis shows that activated Ca 2؉ /calmodulin-dependent in the GOA-1 G o ␣/EGL-30 G q ␣ signaling network (Figure 1a; [3, 9]). To determine the molecular identity of eat-protein kinase II (CaMKII) is suppressed by perturbations of this network, which include loss of 11, we refined the physical map position of eat-11 by using three-factor mapping, and we used transgenic rescue to the GOA-1 G o ␣, DGK-1 diacylglycerol kinase, EAT-16 G protein ␥ subunit–like (GGL)-containing RGS determine that eat-11 encodes GPB-2, an ortholog of the human G␤ 5 protein. G␤ proteins form highly ordered, protein, or an unidentified protein encoded by the gene eat-11 [9]. We cloned eat-11 and report that it seven-bladed propeller structures that are composed of seven WD40 motifs [12, 13]. We identified mutations in encodes the G␤ 5 ortholog GPB-2. G␤ 5 binds specifically to GGL-containing RGS proteins, and the the gpb-2 coding sequence in eight eat-11 alleles (henceforth referred to as gpb-2 alleles). All affected residues lie G␤ 5 /RGS complex can promote the GTP-hydrolyzing activity of G␣ subunits [10, 11]. However, within the conserved core of the GPB-2 WD40 motifs (Figure 1b). Six missense mutations alter residues that little is known about how this interaction affects G protein signaling in vivo. In addition to EAT-16, are conserved among GPB-2, G␤ 5 , and the highly related G␤ 1 protein, and this finding indicates that these muta-the GGL-containing RGS protein EGL-10 participates in G o /G q signaling; EGL-10 appears to tions are likely to cause significant disruption of GPB-2 function. The sa603 and ad541 mutations result in premature truncation of the GPB-2 protein. sa603 creates a stop codon after the second WD40 motif, and this feature We have combined behavioral, electrophysiological, and pharmacological makes it an excellent candidate for a null allele. All of the alleles are recessive, consistent with loss-of-function approaches to show that GPB-2 is a central member of the G o /G q network and that GPB-2 may (lf) mutations. interact with both the EGL-10 and EAT-16 RGS proteins to mediate the opposing activities of G o ␣ gpb-2(lf) mutants exhibit deep body bends during locomo-and G q ␣. These interactions provide a mechanism tion (Figure 2a, upper right panel), a phenotype also seen for the modulation of behavior by antagonistic G in goa-1(lf) mutants …