The mechanism of membrane-translocation of regulator of G-protein signaling (RGS) 8 induced by Gα expression

Abstract

RGS (regulators of G-protein signaling) proteins comprise a large family that modulates heterotrimeric G-protein signaling. This protein family has a common RGS domain and functions as GTPase-activating proteins for the α-subunits of heterotrimeric G-proteins located at the plasma membrane. RGS8 was identified as a neuron-specific RGS protein, which belongs to the B/R4 subfamily. We previously showed that RGS8 protein was translocated to the plasma membrane from the nucleus on coexpression of GTPase-deficient Gαo (GαoQL). Here, we first examined which subtypes of Gα can induce the translocation of RGS8. When the Gαi family was expressed, the translocation of RGS8 did occur. To investigate the mechanism of this translocation, we generated a mutant RGS8 with reduced affinity to Gαo and an RGS-insensitive (RGS-i) mutant of GαoQL. Co-expression experiments with both mutants revealed that disruption of the Gα-RGS8 interaction abolished the membrane-translocation of RGS8 despite the apparent membrane localization of RGS-i GαoQL. These results demonstrated that RGS8 is recruited to the plasma membrane where G-proteins are activated mainly by direct association with Gα.