RGS的表达对视杆光反应的恢复起到限速作用。

RGS expression rate-limits recovery of rod photoresponses.

作者信息

Krispel Claudia M, Chen Desheng, Melling Nathan, Chen Yu-Jiun, Martemyanov Kirill A, Quillinan Nidia, Arshavsky Vadim Y, Wensel Theodore G, Chen Ching-Kang, Burns Marie E

机构信息

Center for Neuroscience, University of California, Davis, 95616, USA.

出版信息

Neuron. 2006 Aug 17;51(4):409-16. doi: 10.1016/j.neuron.2006.07.010.

DOI:10.1016/j.neuron.2006.07.010

PMID:16908407

Abstract

Signaling through G protein-coupled receptors (GPCRs) underlies many cellular processes, yet it is not known which molecules determine the duration of signaling in intact cells. Two candidates are G protein-coupled receptor kinases (GRKs) and Regulators of G protein signaling (RGSs), deactivation enzymes for GPCRs and G proteins, respectively. Here we investigate whether GRK or RGS governs the overall rate of recovery of the light response in mammalian rod photoreceptors, a model system for studying GPCR signaling. We show that overexpression of rhodopsin kinase (GRK1) increases phosphorylation of the GPCR rhodopsin but has no effect on photoresponse recovery. In contrast, overexpression of the photoreceptor RGS complex (RGS9-1.Gbeta5L.R9AP) dramatically accelerates response recovery. Our results show that G protein deactivation is normally at least 2.5 times slower than rhodopsin deactivation, resolving a long-standing controversy concerning the mechanism underlying the recovery of rod visual transduction.

摘要

通过G蛋白偶联受体（GPCRs）进行的信号传导是许多细胞过程的基础，但尚不清楚哪些分子决定完整细胞中信号传导的持续时间。两个候选分子分别是G蛋白偶联受体激酶（GRKs）和G蛋白信号调节剂（RGSs），它们分别是GPCRs和G蛋白的失活酶。在这里，我们研究GRK或RGS是否控制哺乳动物视杆光感受器中光反应的整体恢复速率，视杆光感受器是研究GPCR信号传导的一个模型系统。我们发现，视紫红质激酶（GRK1）的过表达增加了GPCR视紫红质的磷酸化，但对光反应恢复没有影响。相反，光感受器RGS复合物（RGS9-1.Gbeta5L.R9AP）的过表达显著加速了反应恢复。我们的结果表明，G蛋白失活通常比视紫红质失活慢至少2.5倍，解决了关于视杆视觉转导恢复机制的长期争议。