Addition of human melanopsin renders mammalian cells photoresponsive

Addition of human melanopsin renders mammalian cells photoresponsive
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DOI:
10.1038/nature03344
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发表时间:
2005-02-17
期刊:
影响因子:
64.8
通讯作者:
Hankins, MW
Hankins, MW
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Melyan, Z;Tarttelin, EE;Hankins, MW

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少数哺乳动物视网膜神经节细胞作为光感受器,用于调节某些非成像光反应(1 - 10)。这些内在光敏性视网膜神经节细胞表达推定的色素性黑视素(11 - 13)。黑视蛋白基因的消融使这些细胞对光不敏感(14);然而,黑视蛋白在支持细胞光敏性中的确切作用尚未得到证实。在这里,我们表明,异源表达的人黑视素在小鼠旁视细胞系(神经元-2a)是足以使这些细胞的感光。在这样的条件下,黑视素作为感觉色素,通过G蛋白信号级联耦合到天然离子通道,以驱动生理光检测。黑视素光响应依赖于视黄醛的顺式异构体的存在,并且对短波长光选择性敏感。我们还提出了证据表明,黑视素功能作为一种色素在这个系统中,具有内在的光异构酶再生功能,是色移到更长的波长。
A small number of mammalian retinal ganglion cells act as photoreceptors for regulating certain non-image forming photoresponses(1-10). These intrinsically photosensitive retinal ganglion cells express the putative photopigment melanopsin(11-13). Ablation of the melanopsin gene renders these cells insensitive to light(14); however, the precise role of melanopsin in supporting cellular photosensitivity is unconfirmed. Here we show that heterologous expression of human melanopsin in a mouse paraneuronal cell line (Neuro-2a) is sufficient to render these cells photoreceptive. Under such conditions, melanopsin acts as a sensory photopigment, coupled to a native ion channel via a G-protein signalling cascade, to drive physiological light detection. The melanopsin photoresponse relies on the presence of cis-isoforms of retinaldehyde and is selectively sensitive to short-wavelength light. We also present evidence to show that melanopsin functions as a bistable pigment in this system, having an intrinsic photoisomerase regeneration function that is chromatically shifted to longer wavelengths.