Molecular Basis of Circadian Photoreception

Among the recently identified vertebrate opsins, melanopsin has emerged as a photopigment critically involved in the light-mediated regulation of circadian rhythms. Melanopsin is found in a subset of intrinsically photosensitive retinal ganglion cellsipRGCs that directly send photic information to various non-visual light processing brain regions. Melanopsin expression is necessary for the photosensitivity of the ipRGCs and several studies have shown that the melanopsin expressing ipRGCs provide input for photo entrainment, pupillary light reflex, and regulation of the melatonin biosynthetic pathway. Although evidence points towards melanopsin being the functional photo pigment of the ipRGCs, melanopsin may simply function as a photoisomerase, facilitating an as yet unidentified opsin-based photo pigment in the secells. The purpose of this research was to identify whether melanopsin is in fact a photopigment and to elucidate the details of melanopsin photo activation and signaling. We have found that heterologous expression of melanopsin in human embryonic kidney cells HEK293 imparts photosensitivity upon the cell line. With this system, we have found that melanopsin triggers a Gq or a related G protein, activation of phospholipase C, an increase in intracellular calcium from internal calcium stores, and depolarization that may be dependent upon the presence of the canonical transient receptor potential channel, TRPC3.