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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons A/S
2022
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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. |
format | Online Article Text |
id | pubmed-9543991 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley & Sons A/S |
record_format | MEDLINE/PubMed |
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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