A retinal-specific regulator of G-protein signaling interacts with Gαo and accelerates an expressed metabotropic glutamate receptor 6 cascade
A retinal-specific regulator of G-protein signaling interacts with Gαo and accelerates an expressed metabotropic glutamate receptor 6 cascade
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DOI：
10.1523/jneurosci.0492-04.2004
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发表时间：
2004-06-23
影响因子：
5.3
通讯作者：
Vardi, N
中科院分区：
文献类型：
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作者：
Dhingra, A;Faurobert, E;Vardi, N
G(O)是大脑中含量最丰富的G蛋白，但它的调节因子基本上是未知的。在视网膜中，Galpha(O1)在介导代谢性谷氨酸受体6(MGluR6)启动的ON反应中起着重要作用。为了确定GO的相互作用因子，我们进行了酵母双杂交筛选，以具有结构性活性的Galpha(O)为诱饵。筛选发现G蛋白信号转导调节因子Ret-RGS1，我们在转基因细胞和视网膜中与Galpha(O)的免疫共沉淀证实了Ret-RGS1的相互作用。RET-RGS1与mGluR6和Galpha(O1)一起定位于双极神经元的树突顶端。当Ret-RGS1与mGluR6、Galpha(O1)和GIRK(G蛋白门控内向整流钾通道)在非洲爪哇卵母细胞中共表达时，Ret-RGS1以浓度依赖的方式加速了通道对谷氨酸的反应。由于光的开始抑制光感受器释放谷氨酸到ON双极树突上，Ret-RGS1应该会加速ON双极细胞光反应的上升阶段。这将倾向于使其动力学与直接来自配体门控通道的关闭双极的动力学相匹配。
G(o) is the most abundant G-protein in the brain, but its regulators are essentially unknown. In retina, Galpha(o1) is obligatory in mediating the metabotropic glutamate receptor 6 (mGluR6)-initiated ON response. To identify the interactors of Go, we conducted a yeast two-hybrid screen with constituitively active Galpha(o) as a bait. The screen frequently identified a regulator of G-protein signaling (RGS), Ret-RGS1, the interaction of which we confirmed by coimmunoprecipitation with Galpha(o) in transfected cells and in retina. Ret-RGS1 localized to the dendritic tips of ON bipolar neurons, along with mGluR6 and Galpha(o1). When Ret-RGS1 was coexpressed in Xenopus oocytes with mGluR6, Galpha(o1), and a GIRK (G-protein-gated inwardly rectifying K+) channel, it accelerated the deactivation of the channel response to glutamate in a concentration-dependent manner. Because light onset suppresses glutamate release from photoreceptors onto the ON bipolar dendrites, Ret-RGS1 should accelerate the rising phase of the light response of the ON bipolar cell. This would tend to match its kinetics to that of the OFF bipolar that arises directly from ligand-gated channels.