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

In C. elegans, a Go/Gq signaling network regulates locomotion and egg laying [1–8]. Genetic analysis shows that activated Ca2+/calmodulin-dependent protein kinase II (CaMKII) is suppressed by perturbations of this network, which include loss of the GOA-1 Goα, DGK-1 diacylglycerol kinase, EAT-16 G protein γ subunit–like (GGL)-containing RGS protein, or an unidentified protein encoded by the gene eat-11[9]. We cloned eat-11 and report that it encodes the Gβ5 ortholog GPB-2. Gβ5 binds specifically to GGL-containing RGS proteins, and the Gβ5/RGS complex can promote the GTP-hydrolyzing activity of Gα subunits [10, 11]. However, little is known about how this interaction affects G protein signaling in vivo. In addition to EAT-16, the GGL-containing RGS protein EGL-10 participates in Go/Gq signaling; EGL-10 appears to act as an RGS for the GOA-1 Goα, while EAT-16 appears to act as an RGS for the EGL-30 Gqα [4, 5]. We have combined behavioral, electrophysiological, and pharmacological approaches to show that GPB-2 is a central member of the Go/Gq network and that GPB-2 may interact with both the EGL-10 and EAT-16 RGS proteins to mediate the opposing activities of Goα and Gqα. These interactions provide a mechanism for the modulation of behavior by antagonistic G protein networks.