Description
- Abstract:
- Opsins are members of the rhodopsin G-protein coupled receptors (GPCRs) family that mediate phototransduction in both invertebrates and vertebrates. More specifically, humans have nine types of opsins: Blue, green and red opsins (OPN1), OPN2 through 5, peropsin and retinal GPCR (RGR). As critical photoreceptors in several tissues of our own bodies, opsin structures have been extensively characterized, yet functionality of the extra-ocular OPN3 has yet to be elucidated. OPN3 was first discovered in the deep regions of the brain seemingly devoid of light and need for photoreception. In our laboratory, we recently showed that OPN3 is the most highly expressed opsin in human skin. This lends the idea that OPN3 may play a role in dermal light sensing. Furthermore, the presence of other rhodopsin GPCR family members in skin cells raises an intriguing question of whether OPN3 functionally interacts with other skin GPCRs. Here I demonstrated that knocking down OPN3 in human melanocytes leads to an increase in melanin production, intimately linking OPN3 to melanogenic pathways. A key component of melanogenesis is the melanocortin-1 receptor (MC1R), a rhodopsin GPCR family protein. It has been proven numerously that GPCRs, including melanocortin receptors, can form functional heterodimers, which affords the hypothesis that MC1R and OPN3 form a functional heterodimer having a regulatory role in melanin synthesis. To address this hypothesis, I developed several epitope-tagged OPN3 and MC1R constructs and performed co-immunoprecipitation experiments, which showed that MC1R and OPN3 do co-immunoprecipitate in expression systems. Furthermore, these results were confirmed by co-immunoprecipitation of OPN3 and MC1R from human epidermal melanocytes, which endogenously express these proteins. In addition, I demonstrated that expression of OPN3 inhibits the αMSH induced cAMP response of MC1R in a Gαi dependent manner. The work presented here identified a novel function of OPN3 in human skin cells, which give much insight into the underrepresented OPN3 and its functional interactions.
- Notes:
- Thesis (Ph. D.)--Brown University, 2017
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Citation
Ozdeslik, Rana Nur,
"Characterization of OPSIN 3 in Human Skin Cells"
(2017).
Molecular Pharmacology, Physiology, and Biotechnology Theses and Dissertations.
Brown Digital Repository. Brown University Library.
https://doi.org/10.7301/Z0WM1BV2
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Molecular Pharmacology, Physiology, and Biotechnology Theses and Dissertations
Theses and Dissertations for the Molecular Pharmacology, Physiology, and Biotechnology department....