title: Addition of human melanopsin renders mammalian cells photoresponsive.
abstract: A small number of mammalian retinal ganglion cells act as photoreceptors for regulating certain non-image forming photoresponses. These intrinsically photosensitive retinal ganglion cells express the putative photopigment melanopsin. Ablation of the melanopsin gene renders these cells insensitive to light; 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.
authors.affiliation: Department of Visual Neuroscience, Division of Neuroscience and Psychological Medicine, Imperial College London, Charing Cross Hospital Campus, Fulham Palace Road, London W6 8RF, UK.
authors.forename: Z
authors.initials: Z
authors.lastname: Melyan
authors.forename: E E
authors.initials: EE
authors.lastname: Tarttelin
authors.forename: J
authors.initials: J
authors.lastname: Bellingham
authors.forename: R J
authors.initials: RJ
authors.lastname: Lucas
authors.forename: M W
authors.initials: MW
authors.lastname: Hankins
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000528:radiation effects; D002460:Cell Line; D006152:Cyclic GMP / Q000378:metabolism; D015870:Gene Expression; D020962:Heterotrimeric GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008027:Light; D055537:Light Signal Transduction / Q000528:radiation effects*; D051379:Mice; D009474:Neurons / Q000378:metabolism / Q000528:radiation effects*; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D012172:Retinaldehyde / Q000737:chemistry / Q000378:metabolism; D017299:Rod Opsins / Q000235:genetics / Q000378:metabolism*; D000099210:Melanopsin
chemical_list: D006152:Cyclic GMP; D020962:Heterotrimeric GTP-Binding Proteins; D020033:Protein Isoforms; D012172:Retinaldehyde; D017299:Rod Opsins; D000099210:Melanopsin