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Melanocore uptake by keratinocytes occurs through phagocytosis and involves protease‐activated receptor‐2 internalization

In the skin epidermis, melanin is produced and stored within melanosomes in melanocytes, and then transferred to keratinocytes. Different models have been proposed to explain the melanin transfer mechanism, which differ essentially in how melanin is transferred—either in a membrane‐bound melanosome...

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Autores principales: Moreiras, Hugo, Bento‐Lopes, Liliana, Neto, Matilde V., Escrevente, Cristina, Cabaço, Luís C., Hall, Michael J., Ramalho, José S., Seabra, Miguel C., Barral, Duarte C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons A/S 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9543991/
https://www.ncbi.nlm.nih.gov/pubmed/35426185
http://dx.doi.org/10.1111/tra.12843
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author Moreiras, Hugo
Bento‐Lopes, Liliana
Neto, Matilde V.
Escrevente, Cristina
Cabaço, Luís C.
Hall, Michael J.
Ramalho, José S.
Seabra, Miguel C.
Barral, Duarte C.
author_facet Moreiras, Hugo
Bento‐Lopes, Liliana
Neto, Matilde V.
Escrevente, Cristina
Cabaço, Luís C.
Hall, Michael J.
Ramalho, José S.
Seabra, Miguel C.
Barral, Duarte C.
author_sort Moreiras, Hugo
collection PubMed
description In the skin epidermis, melanin is produced and stored within melanosomes in melanocytes, and then transferred to keratinocytes. Different models have been proposed to explain the melanin transfer mechanism, which differ essentially in how melanin is transferred—either in a membrane‐bound melanosome or as a melanosome core, that is, melanocore. Here, we investigated the endocytic route followed by melanocores and melanosomes during internalization by keratinocytes, by comparing the uptake of melanocores isolated from the supernatant of melanocyte cultures, with melanosomes isolated from melanocytes. We show that inhibition of actin dynamics impairs the uptake of both melanocores and melanosomes. Moreover, depletion of critical proteins involved in actin‐dependent uptake mechanisms, namely Rac1, CtBP1/BARS, Cdc42 or RhoA, together with inhibition of Rac1‐dependent signaling pathways or macropinocytosis suggest that melanocores are internalized by phagocytosis, whereas melanosomes are internalized by macropinocytosis. Interestingly, we found that Rac1, Cdc42 and RhoA are differently activated by melanocore or melanosome stimulation, supporting the existence of two distinct routes of melanin internalization. Furthermore, we show that melanocore uptake induces protease‐activated receptor‐2 (PAR‐2) internalization by keratinocytes to a higher extent than melanosomes. Because skin pigmentation was shown to be regulated by PAR‐2 activation, our results further support the melanocore‐based mechanism of melanin transfer and further refine this model, which can now be described as coupled melanocore exo/phagocytosis.
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spelling pubmed-95439912022-10-14 Melanocore uptake by keratinocytes occurs through phagocytosis and involves protease‐activated receptor‐2 internalization Moreiras, Hugo Bento‐Lopes, Liliana Neto, Matilde V. Escrevente, Cristina Cabaço, Luís C. Hall, Michael J. Ramalho, José S. Seabra, Miguel C. Barral, Duarte C. Traffic Research Articles In the skin epidermis, melanin is produced and stored within melanosomes in melanocytes, and then transferred to keratinocytes. Different models have been proposed to explain the melanin transfer mechanism, which differ essentially in how melanin is transferred—either in a membrane‐bound melanosome or as a melanosome core, that is, melanocore. Here, we investigated the endocytic route followed by melanocores and melanosomes during internalization by keratinocytes, by comparing the uptake of melanocores isolated from the supernatant of melanocyte cultures, with melanosomes isolated from melanocytes. We show that inhibition of actin dynamics impairs the uptake of both melanocores and melanosomes. Moreover, depletion of critical proteins involved in actin‐dependent uptake mechanisms, namely Rac1, CtBP1/BARS, Cdc42 or RhoA, together with inhibition of Rac1‐dependent signaling pathways or macropinocytosis suggest that melanocores are internalized by phagocytosis, whereas melanosomes are internalized by macropinocytosis. Interestingly, we found that Rac1, Cdc42 and RhoA are differently activated by melanocore or melanosome stimulation, supporting the existence of two distinct routes of melanin internalization. Furthermore, we show that melanocore uptake induces protease‐activated receptor‐2 (PAR‐2) internalization by keratinocytes to a higher extent than melanosomes. Because skin pigmentation was shown to be regulated by PAR‐2 activation, our results further support the melanocore‐based mechanism of melanin transfer and further refine this model, which can now be described as coupled melanocore exo/phagocytosis. John Wiley & Sons A/S 2022-05-15 2022-06 /pmc/articles/PMC9543991/ /pubmed/35426185 http://dx.doi.org/10.1111/tra.12843 Text en © 2022 The Authors. Traffic published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Moreiras, Hugo
Bento‐Lopes, Liliana
Neto, Matilde V.
Escrevente, Cristina
Cabaço, Luís C.
Hall, Michael J.
Ramalho, José S.
Seabra, Miguel C.
Barral, Duarte C.
Melanocore uptake by keratinocytes occurs through phagocytosis and involves protease‐activated receptor‐2 internalization
title Melanocore uptake by keratinocytes occurs through phagocytosis and involves protease‐activated receptor‐2 internalization
title_full Melanocore uptake by keratinocytes occurs through phagocytosis and involves protease‐activated receptor‐2 internalization
title_fullStr Melanocore uptake by keratinocytes occurs through phagocytosis and involves protease‐activated receptor‐2 internalization
title_full_unstemmed Melanocore uptake by keratinocytes occurs through phagocytosis and involves protease‐activated receptor‐2 internalization
title_short Melanocore uptake by keratinocytes occurs through phagocytosis and involves protease‐activated receptor‐2 internalization
title_sort melanocore uptake by keratinocytes occurs through phagocytosis and involves protease‐activated receptor‐2 internalization
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9543991/
https://www.ncbi.nlm.nih.gov/pubmed/35426185
http://dx.doi.org/10.1111/tra.12843
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