Human nonvisual opsin 3 regulates pigmentation of epidermal melanocytes through functional interaction with melanocortin 1 receptor
| Autor: | Elena Oancea, Melissa M. Trieu, Rana N. Ozdeslik, Lauren E. Olinski, Daniel D. Oprian |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Opsin G protein Melanocyte Cell Line Melanin 030207 dermatology & venereal diseases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine GTP-Binding Proteins Cell Line Tumor medicine Cyclic AMP Humans Cyclic adenosine monophosphate Encephalopsin G protein-coupled receptor Skin Melanins Multidisciplinary integumentary system Pigmentation Cell Membrane Rod Opsins Cell biology 030104 developmental biology medicine.anatomical_structure HEK293 Cells chemistry PNAS Plus Melanocytes Epidermis Receptor Melanocortin Type 1 Melanocortin 1 receptor HeLa Cells Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 116(23) |
| ISSN: | 1091-6490 |
| Popis: | Opsins form a family of light-activated, retinal-dependent, G protein-coupled receptors (GPCRs) that serve a multitude of visual and nonvisual functions. Opsin 3 (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 (HEMs)-the skin cells that produce melanin. The melanin pigment is a critical defense against ultraviolet radiation (UVR), and its production is mediated by the Gαs-coupled melanocortin 1 receptor (MC1R). The physiological function and light sensitivity of OPN3 in melanocytes are yet to be determined. Here, we show that in HEMs, OPN3 acts as a negative regulator of melanin production by modulating the signaling of MC1R. OPN3 negatively regulates the cyclic adenosine monophosphate (cAMP) response evoked by MC1R via activation of the Gαi subunit of G proteins, thus decreasing cellular melanin levels. In addition to their functional relationship, OPN3 and MC1R colocalize at both the plasma membrane and in intracellular structures, and can form a physical complex. Remarkably, OPN3 can bind retinal, but does not mediate light-induced signaling in melanocytes. Our results identify a function for OPN3 in the regulation of the melanogenic pathway in epidermal melanocytes; we have revealed a light-independent function for the poorly characterized OPN3 and a pathway that greatly expands our understanding of melanocyte and skin physiology. |
| Databáze: | OpenAIRE |
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