Prolonged photoresponses in transgenic mouse rods lacking arrestin
Prolonged photoresponses in transgenic mouse rods lacking arrestin
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作者：
Xu, J;Dodd, RL;Chen, J
抑制蛋白是可溶性细胞质蛋白，与G蛋白偶联受体结合，从而关闭G蛋白的激活并终止触发细胞反应的信号通路（1，2）。尽管视觉抑制蛋白已显示出在重构系统中淬灭光激发的磷酸化视紫红质的催化活性（3），但其在完整视杆细胞中的作用仍不清楚，因为磷酸化单独降低视紫红质的催化活性（4-6）。在此，我们记录了来自转基因小鼠的视杆的光电流，其中抑制蛋白基因的一个或两个拷贝被破坏。当抑制蛋白表达减半时，光响应不受影响，表明抑制蛋白结合对于视杆光响应的恢复不是速率限制，如在果蝇中那样（7，8）。在缺乏抑制蛋白的情况下，闪光反应显示出快速的部分恢复，随后是延长的最终阶段。这种行为表明，抑制蛋白独立的机制启动了视紫红质催化活性的淬灭，并且抑制蛋白完成了淬灭。缺乏抑制蛋白的视杆细胞中光反应的强度依赖性进一步表明，尽管抑制蛋白是正常信号终止所必需的，它不直接参与光适应。
Arrestins are soluble cytoplasmic proteins that bind to G-protein-coupled receptors, thus switching off activation of the G protein and terminating the signalling pathway that triggers the cellular response(1,2). Although visual arrestin has been shown to quench the catalytic activity of photoexcited, phosphorylated rhodopsin in a reconstituted system(3), its role in the intact rod cell remains unclear because phosphorylation alone reduces the catalytic activity of rhodopsin(4-6). Here we have recorded photocurrents of rods from transgenic mice in which one or both copies of the arrestin gene were disrupted, Photoresponses were unaffected when arrestin expression was halved, indicating that arrestin binding is not rate limiting for recovery of the rod photoresponse, as it is in Drosophila(7,8). With arrestin absent, the flash response displayed a rapid partial recovery followed by a prolonged final phase, This behaviour indicates that an arrestin-independent mechanism initiates the quench of rhodopsin's catalytic activity and that arrestin completes the quench, The intensity dependence of the photoresponse in rods lacking arrestin further suggests that, although arrestin is required for normal signal termination, it does not participate directly in light adaptation.