Description:

"Light receptors in the dark: opsin 3 signaling in skin and brain"

Opsins form a family of light-activated, retinal-dependent G protein-coupled receptors

(GPCRs) conserved across animal species. The opsins have been studied extensively for their functions in visual phototransduction and circadian entrainment; however, the mechanisms underlying extraocular opsin signaling remain poorly understood. Opsin3 (OPN3 or encephalopsin), initially identified in the brain, remains one of the few members of the mammalian opsin family with unknown function and ambiguous light-absorption properties. We recently discovered that OPN3 is highly expressed in human epidermal melanocytes—the skin cells that produce melanin, a critical defense against solar ultraviolet radiation.  We showed that in human melanocytes OPN3 functions in a light independent manner as a negative regulator of melanin production by modulating the signaling of melanocortin-1 receptor (MC1R). To investigate the function of OPN3 in the brain, we generated a new knock-in mouse model that expresses the fusion protein OPN3-mCherry under the endogenous Opn3 promoter. We used this model to identify a neuronal population in the paraventricular nucleus of the hypothalamus that expresses both OPN3 and melanocortin 4 receptors (MC4R). Our data uncovered a novel cellular mechanism in which OPN3 functions together with MC4R and the inward rectifying potassium channel Kir7.1 to modulate the cellular responses to the endogenous MC4R agonists and neuronal excitability.  

Elena Oancea, PhD
Associate Professor of Medical Science
Department of Molecular Pharmacology, Physiology and Biotechnology
Brown University