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    E-Cadherin mediates UVR- and calcium-induced melanin transfer in human skin cells

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    Publication date
    2017
    Author
    Singh, Suman K.
    Baker, Richard
    Sikkink, Stephen K.
    Nizard, C.
    Schnebert, S.
    Kurfurst, R.
    Tobin, Desmond J.
    Keyword
    E-Cadherin; Melanin transfer;Melanocytes; Keratinocytes; Filopodial; Skin pigmentation; UVR irradiation; Melanogenesis; Calcium selective ORAI1 ion channels; Ca2+ signalling
    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.
    Peer-Reviewed
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    Abstract
    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.
    URI
    http://hdl.handle.net/10454/12481
    Version
    Accepted Manuscript
    Citation
    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.
    Link to publisher’s version
    https://doi.org/10.1111/exd.13395
    Type
    Article
    Collections
    Life Sciences Publications

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