Illumination of the Melanopsin Signaling Cascade

Abstract

Abstract: : Purpose: A small population of intrinsically photosensitive retinal ganglion cells (ipRGCs) plays a key role in the regulation of pineal melatonin synthesis, pupillary light reflex, and circadian photoentrainment. These ipRGCs also express melanopsin, a putative opsin–family photoreceptor, which has been shown to play a role in mediating these non–visual photic responses. The purpose of this study is to characterize the melanopsin signal transduction pathway. Methods: We expressed melanopsin in Xenopus oocytes and tested light induced photocurrent generation in presence of retinal based chromophore. By heterologous expression of candidate signaling components, [pharmacological perturbation and antibody depletion we characterized components of the signal transduction pathway. Results: Oocytes expressing melanopsin generate a photocurrent, which is dependent on presence of a retinal based chromophore. The action spectra of the photocurrent matches that of ipRGCs. Antibody depletion and pharmacological perturbations suggest melanopsin may utilize Gq/G11 mediated signal transduction pathway to open a membrane channel. Conclusions: Melanopsin is a unique mammalian opsin that uses a signal transduction mechanism similar to that of invertebrate opsins.

Keywords: photoreceptors • opsins • signal transduction