E‐cadherin mediates ultraviolet radiation‐ and calcium‐induced melanin transfer in human skin cells |
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| Authors: | Suman K. Singh Richard Baker Stephen K. Sikkink Carine Nizard Sylvianne Schnebert Robin Kurfurst Desmond J. Tobin |
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| Affiliation: | 1. Centre for Skin Sciences, Faculty of Life Sciences, University of Bradford, Bradford, UK;2. LVMH Recherche, F‐45804 Saint Jean de Braye, France |
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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 can be enhanced by filopodi, and by UVR/UVA irradiation, which can upregulate 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. 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 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. |
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| Keywords: | filopodial keratinocytes melanin transfer melanocytes |
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