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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This work was supported by a Wellcome Trust Showcase Award (M.W.H. and R.J.L.) and in part by the BBSRC (R.J.L.) and NSBRI through NASA NCC 9-58 (R.J.L. and R. Foster). We are grateful to R.K. Crouch for the gift of 11-cis retinaldehyde, to R. Douglas for scientific discussions and comments on the manuscript, and to K. Wells for help and advice with cell culture.
The authors declare that they have no competing financial interests.
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Melyan, Z., Tarttelin, E., Bellingham, J. et al. Addition of human melanopsin renders mammalian cells photoresponsive. Nature 433, 741–745 (2005). https://doi.org/10.1038/nature03344
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