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

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Melanins
Keratinocytes
Melanocytes
Melanosomes
Organelles
PAR-2 Receptor
Skin Pigmentation
Endosomes
Endocytosis
Radiation
Staining and Labeling

Keywords

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

Cite this

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title = "Melanin transferred to keratinocytes resides in non-degradative endocytic compartments",
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.",
keywords = "LAMP, lysosomal-associated membrane protein, PAR, PBS, phosphate buffered saline, protease-activated receptor, siRNA, small interfering RNA",
author = "Correia, {Maria S} and Hugo Moreiras and Pereira, {Francisco J C} and Neto, {Matilde V} and Festas, {Tiago C} and Tarafder, {Abul K} and Ramalho, {Jos{\'e} S} and Seabra, {Miguel C} and Barral, {Duarte C}",
note = "Copyright {\circledC} 2017 The Authors. Published by Elsevier Inc. All rights reserved.",
year = "2018",
month = "3",
doi = "10.1016/j.jid.2017.09.042",
language = "English",
volume = "138",
pages = "637--646",
journal = "Journal Of Investigative Dermatology",
issn = "0022-202X",
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TY - JOUR

T1 - Melanin transferred to keratinocytes resides in non-degradative endocytic compartments

AU - Correia, Maria S

AU - Moreiras, Hugo

AU - Pereira, Francisco J C

AU - Neto, Matilde V

AU - Festas, Tiago C

AU - Tarafder, Abul K

AU - Ramalho, José S

AU - Seabra, Miguel C

AU - Barral, Duarte C

N1 - Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2018/3

Y1 - 2018/3

N2 - 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.

AB - 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.

KW - LAMP

KW - lysosomal-associated membrane protein

KW - PAR

KW - PBS

KW - phosphate buffered saline

KW - protease-activated receptor

KW - siRNA

KW - small interfering RNA

U2 - 10.1016/j.jid.2017.09.042

DO - 10.1016/j.jid.2017.09.042

M3 - Article

VL - 138

SP - 637

EP - 646

JO - Journal Of Investigative Dermatology

JF - Journal Of Investigative Dermatology

SN - 0022-202X

IS - 3

ER -