A retinal-specific regulator of G-protein signaling interacts with Gα_o and accelerates an expressed metabotropic glutamate receptor 6 cascade

G_o is the most abundant G-protein in the brain, but its regulators are essentially unknown. In retina, Gα_o1 is obligatory in mediating the metabotropic glutamate receptor 6 (mGluR6)-initiated ON response. To identify the interactors of G_o, we conducted a yeast two-hybrid screen with constituitively active Gα_o as a bait. The screen frequently identified a regulator of G-protein signaling (RGS), Ret-RGS1, the interaction of which we confirmed by coimmunoprecipitation with Gα_o in transfected cells and in retina. Ret-RGS1 localized to the dendritic tips of ON bipolar neurons, along with mGluR6 and Gα_o1. When Ret-RGS1 was coexpressed in Xenopus oocytes with mGluR6, Gα_o1, and a GIRK (G-protein-gated inwardly rectifying K⁺) channel, it accelerated the deactivation of the channel response to glutamate in a concentration-dependent manner. Because light onset suppresses glutamate release from photoreceptors onto the ON bipolar dendrites, Ret-RGS1 should accelerate the rising phase of the light response of the ON bipolar cell. This would tend to match its kinetics to that of the OFF bipolar that arises directly from ligand-gated channels.