The core domain of a new retina specific RGS protein stimulates the GTPase activity of transducin in vitro

GTP hydrolysis by the transducin α subunit is stimulated by a membrane-bound protein. The identity of this GTPase-activating protein (GAP) is not yet known, but the recent identification of a new gene family encoding regulator of G protein signaling (RGS) proteins raises the possibility that the transducin GAP is an RGS protein. Biochemical evidence shows that RGS proteins act as GAPs for α subunits of the G(i) subfamily of G proteins. To identify an RGS protein that could be a GAP for the transducin α subunit, we investigated the expression of RGS proteins in the retina and identified a new RGS domain, RET-RGS-d, which is specifically expressed in the retina. In situ RNA hybridization analyses revealed that RET-RGS-d is expressed in photoreceptor cells as well as in other cells of the retina. Recombinant RET-RGS-d accelerates single turnover hydrolysis of GTP by transducin. We used RET-RGS-d to isolate a full-length cDNA, RET-RGS1, encoding a new RGS protein with a C terminus that corresponds to RET-RGS-d. The N-terminal half of RET-RGS1 contains a putative transmembrane domain and a string of nine cysteines that are potential substrates for multiple palmitoylation. These findings suggest that RET-RGS1 is an integral membrane protein and that it is a candidate for the membrane-associated protein responsible for the GAP activity detected in photoreceptor membranes.