Melanocore uptake by keratinocytes occurs through phagocytosis and involves Protease-activated receptor-2 internalization

Detalhes bibliográficos
Autor(a) principal: Moreiras, Hugo
Data de Publicação: 2022
Outros Autores: Bento-Lopes, Liliana, Neto, Matilde V, Escrevente, Cristina, Cabaço, Luís C, Hall, Michael J, Ramalho, José S, Seabra, Miguel C, Barral, Duarte C
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/140396
Resumo: Funding: The authors would like to thank the scientific and technical assistance from the CEDOC Cell Culture, Flow Cytometry and Microscopy facilities. We also thank the Electron Microscopy Facility of Instituto Gulbenkian de Ciência for technical assistance. The authors also thank Dorothy Bennett and Elena Sviderskaya (St. George's University of London, UK), Susana Lopes (CEDOC, NOVA Medical School) and Paulo Matos (National Health Institute Doutor Ricardo Jorge, Portugal) for the kind gift of reagents and Paulo Matos also for expert advice. This article was supported by the LYSOCIL project. This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No. 811087. This article was also supported by Fundaçao para a Ciência e a Tecnologia ˜ (FCT), Portugal through grant PTDC/BIA-CEL/29765/2017, PhD fellowships to HM, MVN, LBL and LCC (PD/BD/114118/2015, PD/BD/137442/2018, SFRH/BD/131938/2017 and 2020.8812.BD, respectively), the FCT Investigator Program to DCB (IF/00501/2014/ CP1252/CT0001), and FCT Unit iNOVA4Health – UIDB/04462/2020 and UIDP/04462/2020, a programme financially supported by FCT / Ministério da Ciência, Tecnologia e Ensino Superior, through national funds.
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spelling Melanocore uptake by keratinocytes occurs through phagocytosis and involves Protease-activated receptor-2 internalizationmacropinocytosismelanocoremelanosomesphagocytosisprotease-activated receptor-2Funding: The authors would like to thank the scientific and technical assistance from the CEDOC Cell Culture, Flow Cytometry and Microscopy facilities. We also thank the Electron Microscopy Facility of Instituto Gulbenkian de Ciência for technical assistance. The authors also thank Dorothy Bennett and Elena Sviderskaya (St. George's University of London, UK), Susana Lopes (CEDOC, NOVA Medical School) and Paulo Matos (National Health Institute Doutor Ricardo Jorge, Portugal) for the kind gift of reagents and Paulo Matos also for expert advice. This article was supported by the LYSOCIL project. This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No. 811087. This article was also supported by Fundaçao para a Ciência e a Tecnologia ˜ (FCT), Portugal through grant PTDC/BIA-CEL/29765/2017, PhD fellowships to HM, MVN, LBL and LCC (PD/BD/114118/2015, PD/BD/137442/2018, SFRH/BD/131938/2017 and 2020.8812.BD, respectively), the FCT Investigator Program to DCB (IF/00501/2014/ CP1252/CT0001), and FCT Unit iNOVA4Health – UIDB/04462/2020 and UIDP/04462/2020, a programme financially supported by FCT / Ministério da Ciência, Tecnologia e Ensino Superior, through national funds.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, i.e., 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 internalization 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. Since 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.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNMoreiras, HugoBento-Lopes, LilianaNeto, Matilde VEscrevente, CristinaCabaço, Luís CHall, Michael JRamalho, José SSeabra, Miguel CBarral, Duarte C2022-06-20T22:22:12Z2022-062022-06-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/140396eng1398-9219PURE: 43329076https://doi.org/10.1111/tra.12843info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:17:31Zoai:run.unl.pt:10362/140396Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:49:38.686196Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv 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
spellingShingle Melanocore uptake by keratinocytes occurs through phagocytosis and involves Protease-activated receptor-2 internalization
Moreiras, Hugo
macropinocytosis
melanocore
melanosomes
phagocytosis
protease-activated receptor-2
title_short 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_sort Melanocore uptake by keratinocytes occurs through phagocytosis and involves Protease-activated receptor-2 internalization
author Moreiras, Hugo
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_role author
author2 Bento-Lopes, Liliana
Neto, Matilde V
Escrevente, Cristina
Cabaço, Luís C
Hall, Michael J
Ramalho, José S
Seabra, Miguel C
Barral, Duarte C
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Centro de Estudos de Doenças Crónicas (CEDOC)
RUN
dc.contributor.author.fl_str_mv 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
dc.subject.por.fl_str_mv macropinocytosis
melanocore
melanosomes
phagocytosis
protease-activated receptor-2
topic macropinocytosis
melanocore
melanosomes
phagocytosis
protease-activated receptor-2
description Funding: The authors would like to thank the scientific and technical assistance from the CEDOC Cell Culture, Flow Cytometry and Microscopy facilities. We also thank the Electron Microscopy Facility of Instituto Gulbenkian de Ciência for technical assistance. The authors also thank Dorothy Bennett and Elena Sviderskaya (St. George's University of London, UK), Susana Lopes (CEDOC, NOVA Medical School) and Paulo Matos (National Health Institute Doutor Ricardo Jorge, Portugal) for the kind gift of reagents and Paulo Matos also for expert advice. This article was supported by the LYSOCIL project. This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No. 811087. This article was also supported by Fundaçao para a Ciência e a Tecnologia ˜ (FCT), Portugal through grant PTDC/BIA-CEL/29765/2017, PhD fellowships to HM, MVN, LBL and LCC (PD/BD/114118/2015, PD/BD/137442/2018, SFRH/BD/131938/2017 and 2020.8812.BD, respectively), the FCT Investigator Program to DCB (IF/00501/2014/ CP1252/CT0001), and FCT Unit iNOVA4Health – UIDB/04462/2020 and UIDP/04462/2020, a programme financially supported by FCT / Ministério da Ciência, Tecnologia e Ensino Superior, through national funds.
publishDate 2022
dc.date.none.fl_str_mv 2022-06-20T22:22:12Z
2022-06
2022-06-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/140396
url http://hdl.handle.net/10362/140396
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1398-9219
PURE: 43329076
https://doi.org/10.1111/tra.12843
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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