Rab11b mediates melanin transfer between donor melanocytes and acceptor keratinocytes via coupled exo/endocytosis

J Invest Dermatol. 2014 Apr;134(4):1056-1066. doi: 10.1038/jid.2013.432. Epub 2013 Oct 18.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Coculture Techniques
  • Endocytosis
  • Exocytosis
  • Gene Expression Regulation
  • Humans
  • Immunohistochemistry
  • Keratinocytes / cytology
  • Keratinocytes / metabolism*
  • Lysosomal Membrane Proteins / metabolism
  • Melanins / metabolism*
  • Melanocytes / cytology
  • Melanocytes / metabolism*
  • Membrane Glycoproteins / metabolism
  • Microscopy, Electron
  • Microscopy, Electron, Transmission
  • Microscopy, Fluorescence
  • Oxidoreductases / metabolism
  • RNA, Small Interfering / metabolism
  • Skin / metabolism*
  • Skin / ultrastructure
  • rab GTP-Binding Proteins / metabolism*
  • rab27 GTP-Binding Proteins

Substances

  • LAMP1 protein, human
  • Lysosomal Membrane Proteins
  • Melanins
  • Membrane Glycoproteins
  • RNA, Small Interfering
  • rab27 GTP-Binding Proteins
  • Oxidoreductases
  • TYRP1 protein, human
  • rab11 protein
  • RAB27A protein, human
  • rab GTP-Binding Proteins