Regulator of G Protein Signaling 8 (RGS8) Requires Its NH₂ Terminus for Subcellular Localization and Acute Desensitization of G Protein-gated K⁺ Channels

Functional roles of the NH₂-terminal region of RGS (regulators of G protein signaling) 8 in G protein signaling were studied. The deletion of the NH₂-terminal region of RGS8 (ΔNRGS8) resulted in a partial loss of the inhibitory function in pheromone response of yeasts, although Gα binding was not affected. To examine roles in subcellular distribution, we coexpressed two fusion proteins of RGS8-RFP and ΔNRGS8-GFP in DDT1MF2 cells. RGS8-RFP was highly concentrated in nuclei of unstimulated cells. Coexpression of constitutively active Gα_o resulted in translocation of RGS8 protein to the plasma membrane. In contrast, ΔNRGS8-GFP was distributed diffusely through the cytoplasm in the presence or absence of active Gα_o. When coexpressed with G protein-gated inwardly rectifying K⁺ channels, ΔNRGS8 accelerated both turning on and off similar to RGS8. Acute desensitization of G protein-gated inwardly rectifying K⁺ current observed in the presence of RGS8, however, was not induced by ΔNRGS8. Thus, we, for the first time, showed that the NH₂ terminus of RGS8 contributes to the subcellular localization and to the desensitization of the G protein-coupled response.