Gβ5-RGS complexes co-localize with mGluR6 in retinal ON-bipolar cells
Gβ5-RGS complexes co-localize with mGluR6 in retinal ON-bipolar cells
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DOI：
10.1111/j.1460-9568.2007.05867.x
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发表时间：
2007-11-01
影响因子：
3.4
通讯作者：
Duvoisin, Robert M.
中科院分区：
文献类型：
--
作者：
Morgans, Catherine W.;Liu, Weiwei;Duvoisin, Robert M.
G蛋白偶联反应的时间过程主要由G蛋白α亚基水解GTP的动力学决定，G蛋白α亚基与G蛋白信号调节因子（RGS）蛋白相互作用加速水解。脊椎动物视网膜的ON-双极细胞的光响应需要G蛋白G α 0的快速失活，G蛋白G α 0在黑暗中被它们的树突尖端中的代谢型谷氨酸受体mGluR 6激活。然而，目前尚不清楚哪种RGS蛋白可能负责快速失活动力学。通过免疫荧光和免疫共沉淀，我们已经确定了复合物的G α O-选择性RGS蛋白RGS 7和RGS 11，其专性结合伙伴，G β 5，是本地化的树突状尖端的小鼠杆和锥ON双极细胞，沿着与mGluR 6。实验使用前和突触后标记物，和解离的双极细胞制备，清楚地确定了这些复合物的位置作为ON双极细胞树突状尖端，而不是相邻的感光末梢或水平细胞树突。在缺乏mGluR 6的小鼠中，RGS 11，RGS 7和G β 5的分布远离树突尖端，这意味着与mGluR 6的功能关系。G β 5-RGS 7和G β 5-RGS 11与mGluR 6的精确共定位，以及定位对mGluR 6存在的依赖性，表明G β 5-RGS 7和G β 5-RGS 11在mGluR 6信号转导途径中特异性地起作用，其中它们可以刺激G α 0的GT3活性，从而加速ON-双极细胞光响应，以类似于G β 5-RGS 9 -1复合物加速光感受器光反应的方式。
The time course of G-protein-coupled responses is largely determined by the kinetics of GTP hydrolysis by the G protein alpha subunit, which is accelerated by interaction with regulator of G-protein signaling (RGS) proteins. Light responses of ON-bipolar cells of the vertebrate retina require rapid inactivation of the G protein G alpha o, which is activated in the dark by metabotropic glutamate receptor, mGluR6, in their dendritic tips. It is not yet known, however, which RGS protein(s) might be responsible for rapid inactivation kinetics. By immunofluorescence and co-immunoprecipitation, we have identified complexes of the G alpha o-selective RGS proteins RGS7 and RGS11, with their obligate binding partner, G beta 5, that are localized to the dendritic tips of murine rod and cone ON-bipolar cells, along with mGluR6. Experiments using pre- and post-synaptic markers, and a dissociated bipolar cell preparation, clearly identified the location of these complexes as the ON-bipolar cell dendritic tips and not the adjacent photoreceptor terminals or horizontal cell dendrites. In mice lacking mGluR6, the distribution of RGS11, RGS7 and G beta 5 shifts away from the dendritic tips, implying a functional relationship with mGluR6. The precise co-localization of G beta 5-RGS7 and G beta 5-RGS11 with mGluR6, and the dependence of localization on the presence of mGluR6, suggests that G beta 5-RGS7 and G beta 5-RGS11 function specifically in the mGluR6 signal transduction pathway, where they may stimulate the GTPase activity of G alpha o, thus accelerating the ON-bipolar cell light response, in a manner analogous to the acceleration of photoreceptor light responses by the G beta 5-RGS9-1 complex.