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The transfer of melanin from melanocytes to keratinocytes is a crucial process underlying maintenance of skin pigmentation and photoprotection against UV damage. Here, we present evidence supporting coupled exocytosis of the melanin core, or melanocore, by melanocytes and subsequent endocytosis by keratinocytes as a predominant mechanism of melanin transfer. Electron microscopy analysis of human skin samples revealed three lines of evidence supporting this: (1) the presence of melanocores in the extracellular space; (2) within keratinocytes, melanin was surrounded by a single membrane; and (3) this membrane lacked the melanosomal membrane protein tyrosinase-related protein 1 (TYRP1). Moreover, co-culture of melanocytes and keratinocytes suggests that melanin exocytosis is specifically induced by keratinocytes. Furthermore, depletion of Rab11b, but not Rab27a, caused a marked decrease in both keratinocyte-stimulated melanin exocytosis and transfer to keratinocytes. Thus, we propose that the predominant mechanism of melanin transfer is keratinocyte-induced exocytosis, mediated by Rab11b through remodeling of the melanosome membrane, followed by subsequent endocytosis by keratinocytes.

Original publication

DOI

10.1038/jid.2013.432

Type

Journal article

Journal

J Invest Dermatol

Publication Date

04/2014

Volume

134

Pages

1056 - 1066

Keywords

Coculture Techniques, Endocytosis, Exocytosis, Gene Expression Regulation, Humans, Immunohistochemistry, Keratinocytes, Lysosome-Associated Membrane Glycoproteins, Melanins, Melanocytes, Membrane Glycoproteins, Microscopy, Electron, Microscopy, Electron, Transmission, Microscopy, Fluorescence, Oxidoreductases, RNA, Small Interfering, Skin, rab GTP-Binding Proteins