Melanopsin Is Highly Resistant to Light and Chemical Bleaching in Vivo
Melanopsin Is Highly Resistant to Light and Chemical Bleaching in Vivo
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DOI：
10.1074/jbc.m111.325969
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发表时间：
2012-06-15
影响因子：
4.8
通讯作者：
Van Gelder, Russell N.
中科院分区：
文献类型：
--
作者：
Sexton, Timothy J.;Golczak, Marcin;Van Gelder, Russell N.
黑视素是哺乳动物内在光敏视网膜神经节细胞的色素，在那里它有助于昼夜节律的光夹带和瞳孔光反应。先前的工作已经表明，黑视蛋白光循环与视紫红质所使用的光循环无关（Tu，D. C.的方法，欧文斯湖一、安德森，L.，Golczak，M.，道尔，S。E、McCall，M.，Menaker，M.，Palczewski，K.，和货车Gelder，R. N.（2006）独立于视觉类维生素A周期的内部视网膜光感受。Proc. Natl. Acad. Sci. U.S.A.103，10426-10431）。在这里，我们确定的能力，脱辅基黑视蛋白，形成离体紫外线漂白，使用选定的发色团。我们发现，9-顺式-视黄醛，而不是全反式-视黄醛或9-顺式-视黄醇，能够在漂白后恢复光依赖性ipRGC活性。在完全漂白视杆细胞和视锥细胞的条件下，黑视素对可见光谱光漂白和羟胺化学漂白都具有高度抗性。这些结果表明，黑视素光循环可以独立于视杆细胞和视锥细胞的光循环发挥作用，并且脱辅基黑视素具有强烈的偏好结合顺式-视黄醛以产生功能性色素。这些数据支持一种模型，其中视网膜连续共价结合黑视蛋白，并可能通过可逆的，可逆的机制发挥作用。
Melanopsin is the photopigment of mammalian intrinsically photosensitive retinal ganglion cells, where it contributes to light entrainment of circadian rhythms, and to the pupillary light response. Previous work has shown that the melanopsin photocycle is independent of that used by rhodopsin (Tu, D. C., Owens, L. A., Anderson, L., Golczak, M., Doyle, S. E., McCall, M., Menaker, M., Palczewski, K., and Van Gelder, R. N. (2006) Inner retinal photoreception independent of the visual retinoid cycle. Proc. Natl. Acad. Sci. U.S.A. 103, 10426-10431). Here we determined the ability of apo-melanopsin, formed by ex vivo UV light bleaching, to use selected chromophores. We found that 9-cis-retinal, but not all-trans-retinal or 9-cis-retinol, is able to restore light-dependent ipRGC activity after bleaching. Melanopsin was highly resistant to both visible-spectrum photic bleaching and chemical bleaching with hydroxylamine under conditions that fully bleach rod and cone photoreceptor cells. These results suggest that the melanopsin photocycle can function independently of both rod and cone photocycles, and that apo-melanopsin has a strong preference for binding cis-retinal to generate functional pigment. The data support a model in which retinal is continuously covalently bound to melanopsin and may function through a reversible, bistable mechanism.