yes / Skin pigmentation is directed by epidermal-melanin units, characterized by long-lived and dendritic epidermal melanocytes (MC) that interact with viable keratinocytes (KC) to contribute melanin to the epidermis. Previously we reported that MC:KC contact is required for melanosome transfer, that this can be enhanced by filopodial and by UVR/UVA irradiation, which can up-regulate melanosome transfer via Myosin X-mediated control of MC filopodia. Both MC and KC express Ca2+-dependent E-cadherins. These homophilic adhesion contacts induce transient increases in intra-KC Ca2+, while ultraviolet radiation (UVR) raises intra-MC Ca2+ via calcium selective ORAI1 ion channels; both are associated with regulating melanogenesis.
However, how Ca2+ triggers melanin transfer remains unclear, and here we evaluated the role of E-Cadherin in UVR-mediated melanin transfer in human skin cells. MC and KC in human epidermis variably express filopodia-associated E-Cadherin, Cdc42, VASP and β-catenin, all of which were upregulated by UVR/UVA in human MC in vitro. Knockdown of E-cadherin revealed that this cadherin is essential for UVR-induced MC filopodia formation and melanin transfer. Moreover, Ca2+ induced a dose-dependent increase in filopodia formation and melanin transfer, as well as increased β-catenin, Cdc42, Myosin X, and E-Cadherin expression in these skin cells. Together these data suggest that filopodial proteins and E-Cadherin, which are upregulated by intracellular (UVR-stimulated) and extracellular Ca2+ availability, are required for filopodia formation and melanin transfer. This may open new avenues to explore how Ca2+ signalling influences human pigmentation.
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/12481 |
| Date | 21 June 2017 |
| Creators | Singh, Suman K., Baker, Richard, Sikkink, Stephen, Nizard, C., Schnebert, S., Kurfurst, R., Tobin, Desmond J. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Accepted Manuscript |
| Rights | © 2017 Wiley Periodicals, Inc. Full-text reproduced in accordance with the publisher’s self-archiving policy. This is the peer reviewed version of the following article: "Singh SK, Baker R, Sikkink SK, Nizard C, Schnebert S, Kurfurst R and Tobin DJ (2017) E-Cadherin mediates UVR- and calcium-induced melanin transfer in human skin cells. Experimental Dermatology. 26(11): 1125-1133" which has been published in final form at https://doi.org/10.1111/exd.13395. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. |
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