Melanin transferred to keratinocytes resides in non-degradative endocytic compartments

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Abstract

Melanin transfer from melanocytes to keratinocytes and subsequent accumulation in the supra-nuclear region is a critical process in skin pigmentation and protection against ultraviolet radiation. We have previously proposed that the main mode of transfer between melanocytes and keratinocytes is through exo/endocytosis of the melanosome core, termed melanocore. In this study, we developed an in vitro uptake assay using melanocores secreted by melanocytes. We show that the uptake of melanocores, but not melanosomes, by keratinocytes is Protease-activated receptor (PAR)-2-dependent. Furthermore, we found that the silencing of the early endocytic regulator Rab5b, but not the late endocytic regulators Rab7a or Rab9a, significantly impairs melanocore uptake by keratinocytes. Following uptake, we observed that melanin accumulates in compartments that are positive for both early and late endocytic markers. We found that melanin does not localize to either highly degradative or acidic organelles, as assessed by LysoTracker and DQ-BSA staining, despite the abundance of these types of organelles within keratinocytes. Therefore, we propose that melanocore uptake leads to storage of melanin within keratinocytes in hybrid endocytic compartments that are not highly acidic or degradative. By avoiding lysosomal degradation, these specialized endosomes may allow melanin to persist within keratinocytes for long periods.

Original languageEnglish
Pages (from-to)637-646
Number of pages10
JournalJournal Of Investigative Dermatology
Volume138
Issue number3
Early online date23 Oct 2017
DOIs
Publication statusPublished - Mar 2018

Keywords

  • LAMP
  • lysosomal-associated membrane protein
  • PAR
  • PBS
  • phosphate buffered saline
  • protease-activated receptor
  • siRNA
  • small interfering RNA

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