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Nature 433, 741-745 (17 February 2005) | doi:10.1038/nature03344; Received 21 October 2004; Accepted 12 January 2005; Published online 26 January 2005
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Addition of human melanopsin renders mammalian cells photoresponsive
Z. Melyan1, E. E. Tarttelin1,2, J. Bellingham2, R. J. Lucas2 & M. W. Hankins1
- Department of Visual Neuroscience, Division of Neuroscience and Psychological Medicine, Imperial College London, Charing Cross Hospital Campus, Fulham Palace Road, London W6 8RF, UK
- Faculty of Life Sciences, Michael Smith Building, University of Manchester, Manchester M13 9PT, UK
Correspondence to: R. J. Lucas2M. W. Hankins1 Correspondence and requests for materials should be addressed to R.J.L. (Email: robert.lucas@manchester.ac.uk) or M.W.H. (Email: m.hankins@imperial.ac.uk).
Abstract
A small number of mammalian retinal ganglion cells act as photoreceptors for regulating certain non-image forming photoresponses1, 2, 3, 4, 5, 6, 7, 8, 9, 10. These intrinsically photosensitive retinal ganglion cells express the putative photopigment melanopsin11, 12, 13. Ablation of the melanopsin gene renders these cells insensitive to light14; 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.
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