Qiu Xudong, Kumbalasiri Tida, Carlson Stephanie M, Wong Kwoon Y, Krishna Vanitha, Provencio Ignacio, Berson David M
Department of Neuroscience, Box 1953, Brown University, Providence, Rhode Island 02912-1953, USA.
Nature. 2005 Feb 17;433(7027):745-9. doi: 10.1038/nature03345. Epub 2005 Jan 26.
Melanopsin has been proposed to be the photopigment of the intrinsically photosensitive retinal ganglion cells (ipRGCs); these photoreceptors of the mammalian eye drive circadian and pupillary adjustments through direct projections to the brain. Their action spectrum (lambda(max) approximately 480 nm) implicates an opsin and melanopsin is the only opsin known to exist in these cells. Melanopsin is required for ipRGC photosensitivity and for behavioural photoresponses that survive disrupted rod and cone function. Heterologously expressed melanopsin apparently binds retinaldehyde and mediates photic activation of G proteins. However, its amino-acid sequence differs from vertebrate photosensory opsins and some have suggested that melanopsin may be a photoisomerase, providing retinoid chromophore to an unidentified opsin. To determine whether melanopsin is a functional sensory photopigment, here we transiently expressed it in HEK293 cells that stably expressed TRPC3 channels. Light triggered a membrane depolarization in these cells and increased intracellular calcium. The light response resembled that of ipRGCs, with almost identical spectral sensitivity (lambda(max) approximately 479 nm). The phototransduction pathway included Gq or a related G protein, phospholipase C and TRPC3 channels. We conclude that mammalian melanopsin is a functional sensory photopigment, that it is the photopigment of ganglion-cell photoreceptors, and that these photoreceptors may use an invertebrate-like phototransduction cascade.
有人提出，黑视蛋白是内在光敏性视网膜神经节细胞（ipRGCs）的光色素；哺乳动物眼睛的这些光感受器通过直接投射到大脑来驱动昼夜节律和瞳孔调节。它们的作用光谱（λmax约为480nm）表明存在一种视蛋白，而黑视蛋白是已知存在于这些细胞中的唯一视蛋白。黑视蛋白是ipRGC光敏感性以及在视杆和视锥功能受损后仍能存活的行为光反应所必需的。在异源细胞中表达的黑视蛋白显然能结合视黄醛并介导G蛋白的光激活。然而，其氨基酸序列与脊椎动物的光感觉视蛋白不同，一些人认为黑视蛋白可能是一种光异构酶，为一种未鉴定的视蛋白提供类视黄醇发色团。为了确定黑视蛋白是否是一种功能性的感觉光色素，我们在此将其瞬时表达于稳定表达TRPC3通道的HEK293细胞中。光触发了这些细胞的膜去极化并增加了细胞内钙。光反应类似于ipRGCs的反应，光谱敏感性几乎相同（λmax约为479nm）。光转导途径包括Gq或一种相关的G蛋白、磷脂酶C和TRPC3通道。我们得出结论，哺乳动物黑视蛋白是一种功能性的感觉光色素，它是神经节细胞光感受器的光色素，并且这些光感受器可能使用类似无脊椎动物的光转导级联。
