Regulator of G protein signaling 8 (RGS8) requires its NH2 terminus for subcellular localization and acute desensitization of G protein-gated K+ channels

被引:56
作者
Saitoh, O
Masuho, I
Terakawa, I
Nomoto, S
Asano, T
Kubo, Y
机构
[1] Tokyo Metropolitan Inst Neurosci, Dept Mol & Cellular Neurobiol, Fuchu, Tokyo 1838526, Japan
[2] Hamamatsu Univ Sch Med, Hamamatsu, Aichi 4313192, Japan
[3] Jichi Med Sch, Dept Hlth Sci, Minami Kawachi, Tochigi 3290498, Japan
[4] CREST, Minami Kawachi, Tochigi 3290498, Japan
[5] Aichi Human Serv Ctr, Inst Dev Res, Dept Biochem, Kasugai, Aichi 48003, Japan
[6] Tokyo Metropolitan Inst Neurosci, Dept Neurophysiol, Fuchu, Tokyo 1838526, Japan
[7] Tokyo Med & Dent Univ, Grad Sch Med, Dept Physiol, Bunkyo Ku, Tokyo 1138519, Japan
[8] Tokyo Med & Dent Univ, Fac Med, Bunkyo Ku, Tokyo 1138519, Japan
关键词
D O I
10.1074/jbc.M006917200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 (Delta NRGS8) resulted in a partial loss of the inhibitory function in pheromone response of yeasts, although G alpha binding was not affected. To examine roles in subcellular distribution, we coexpressed two fusion proteins of RGS8-RFP and Delta NRGS8-GFP in DDT1MF2 cells. RGS8-RFP was highly concentrated in nuclei of unstimulated cells. Coexpression of constitutively active G alpha (o), resulted in translocation of RGS8 protein to the plasma membrane. In contrast, Delta NRGS8-GFP was distributed diffusely through the cytoplasm in the presence or absence of active G alpha (o). When coexpressed with G protein-gated inwardly rectifying K+ channels, Delta NRGS8 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 Delta NRGS8. 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.
引用
收藏
页码:5052 / 5058
页数:7
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