Nuclear localization of the G protein [beta]5/R7-regulator of G protein signaling protein complex is dependent on R7 binding protein: 1

J. Neurochem. (2010) 113, 1101-1112. The neuronally expressed Gβ5 subunit is the most structurally divergent among heterotrimeric Gβ isoforms and unique in its ability to heterodimerize with the R7 subfamily of regulator of G protein signaling (RGS) proteins. The complex between Gβ5 and R7-type RGS proteins targets the cell nucleus by an unknown mechanism. Although the nuclear targeting of the Gβ5/R7-RGS complex is proposed to involve the binding of R7-binding protein (R7BP), this theory is challenged by the observations that endogenous R7BP is palmitoylated, co-localizes strongly with the plasma membrane, and has never been identified in the cytosol or nucleus of native neurons or untreated cultured cells. We show here mutant RGS7 lacking the N-terminal Disheveled, EGL-10, Pleckstrin homology domain is expressed in transfected cells but, unlike wild-type RGS7, is excluded from the cell nucleus. As the Disheveled, EGL-10, Pleckstrin homology domain is essential for R7BP binding to RGS7, we studied the subcellular localization of Gβ5 in primary neurons and brain from mice deficient in R7BP. The level of endogenous nuclear Gβ5 and RGS7 in neurons and brains from R7BP knockout mice is reduced by 50-70%. These results suggest that R7BP contributes significantly to the nuclear localization of endogenous Gβ5/R7-RGS complex in brain.