Protein Gq Modulates Termination of Phototransduction and Prevents Retinal Degeneration
Protein Gq Modulates Termination of Phototransduction and Prevents Retinal Degeneration
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DOI：
10.1074/jbc.m112.339895
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发表时间：
2012-04-20
影响因子：
4.8
通讯作者：
Han, Junhai
中科院分区：
文献类型：
--
作者：
Hu, Wen;Wan, Didi;Han, Junhai
适当终止光转导级联对于光感受器实现高时间分辨率和防止过度Ca 2+诱导的细胞毒性至关重要。使用遗传筛选来鉴定果蝇中有缺陷的光响应突变体，我们分离并鉴定了一种新的G alpha（q）突变等位基因，该等位基因在激活和失活方面都存在缺陷。我们发现，G（q）调制光响应的终止和metarhodopsin/G（q）的相互作用影响随后的arrestin-rhodopsin（Arr 2-Rh 1）的结合，介导的metarhodopsin的失活。我们进一步表明，G α（q）突变体经历光依赖性视网膜变性，这是由于稳定的Arr 2-Rh 1复合物的缓慢积累。我们的研究揭示了Gq在介导光反应终止和预防视网膜变性中的作用。该通路可能代表了G蛋白偶联受体信号传导的一般快速反馈调节。
Appropriate termination of the phototransduction cascade is critical for photoreceptors to achieve high temporal resolution and to prevent excessive Ca2+-induced cell toxicity. Using a genetic screen to identify defective photoresponse mutants in Drosophila, we isolated and identified a novel G alpha(q) mutant allele, which has defects in both activation and deactivation. We revealed that G(q) modulates the termination of the light response and that metarhodopsin/G(q) interaction affects subsequent arrestin-rhodopsin (Arr2-Rh1) binding, which mediates the deactivation of metarhodopsin. We further showed that the G alpha(q) mutant undergoes light-dependent retinal degeneration, which is due to the slow accumulation of stable Arr2-Rh1 complexes. Our study revealed the roles of Gq in mediating photoresponse termination and in preventing retinal degeneration. This pathway may represent a general rapid feedback regulation of G protein-coupled receptor signaling.