Tateyama Michihiro, Kubo Yoshihiro
Department of Molecular Physiology, Division of Biophysics and Neurobiology, National Institute for Physiological Sciences, Myodaiji, Okazaki, Japan.
J Neurochem. 2008 Nov;107(4):1036-46. doi: 10.1111/j.1471-4159.2008.05672.x. Epub 2008 Sep 11.
The signaling property of metabotropic glutamate receptor 1alpha (mGlu1alpha) is different from that of short-form splice variants. This could be caused by the exposure of a cluster of positively charged amino acid residues, RRKK, in the proximal C-tail which is thought to be masked by the long C-tail of mGlu1alpha. We found that the RRKK residues, when exposed, attenuate Gq coupling and decrease the basal activity and the surface expression of mGlu1, in agreement with previous results. Moreover, these residues abolish the Gi/o coupling of mGlu1, but do not affect glutamate-induced dimeric rearrangement and protein kinase A-dependent modulation of mGlu1. These results suggest that the RRKK residues do not inhibit the conformational change upon glutamate binding and protein accessibility to the intracellular loops where G-protein coupling occurs, but rather act as an inhibitory domain against G-protein coupling in a different manner depending on the type of G protein.
代谢型谷氨酸受体1α（mGlu1α）的信号传导特性与短形式剪接变体不同。这可能是由于在近端C末端暴露了一簇带正电荷的氨基酸残基RRKK，而该区域被认为被mGlu1α的长C末端所掩盖。我们发现，RRKK残基暴露后会减弱Gq偶联，并降低mGlu1的基础活性和表面表达，这与之前的结果一致。此外，这些残基消除了mGlu1的Gi/o偶联，但不影响谷氨酸诱导的二聚体重排以及蛋白激酶A对mGlu1的依赖性调节。这些结果表明，RRKK残基不会抑制谷氨酸结合时的构象变化以及G蛋白偶联发生的细胞内环的蛋白可及性，而是根据G蛋白的类型以不同方式作为针对G蛋白偶联的抑制结构域。
