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^{1,2,3,4,5,6,7,8,9,10}. These intrinsically photosensitive retinal ganglion cells express the putative photopigment melanopsin^11,12,13. 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.