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Melanin’s Journey from Melanocytes to Keratinocytes: Uncovering the Molecular Mechanisms of Melanin Transfer and Processing

2023-07-10Artigo científico Acesso aberto
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dc.contributor.authorBento-Lopes, Liliana
dc.contributor.authorCabaço, Luís C.
dc.contributor.authorCabaço, Luís C.
dc.contributor.authorCharneca, João
dc.contributor.authorNeto, Matilde V.
dc.contributor.authorSeabra, Miguel C.
dc.contributor.authorC Seabra, Miguel
dc.contributor.authorBarral, Duarte C.
dc.contributor.authorC. Barral, Duarte
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutioniNOVA4Health - pólo NMS
dc.contributor.pblMDPI - Multidisciplinary Digital Publishing Institute
dc.date.accessioned2023-07-27T22:15:45Z
dc.date.available2023-07-27T22:15:45Z
dc.date.issued2023-07-10
dc.descriptionFunding This research was funded by Fundação para a Ciência e a Tecnologia (Portugal) grant number PTDC/BIA-CEL/29765/2017 and Ph.D. fellowships to L.B.-L., L.C.C., M.V.N. and J.C. (numbers SFRH/BD/131938/2017, 2020.08812.BD, PD/BD/137442/2018, and PD/BD/136905/2018, respectively). This work was also supported by iNOVA4Health—UIDB/04462/2020 and UIDP/04462/2020—and by the Associated Laboratory LS4FUTURE (LA/P/0087/2020), two programs financially supported by Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior (Portugal).
dc.description.abstractSkin pigmentation ensures efficient photoprotection and relies on the pigment melanin, which is produced by epidermal melanocytes and transferred to surrounding keratinocytes. While the molecular mechanisms of melanin synthesis and transport in melanocytes are now well characterized, much less is known about melanin transfer and processing within keratinocytes. Over the past few decades, distinct models have been proposed to explain how melanin transfer occurs at the cellular and molecular levels. However, this remains a debated topic, as up to four different models have been proposed, with evidence presented supporting each. Here, we review the current knowledge on the regulation of melanin exocytosis, internalization, processing, and polarization. Regarding the different transfer models, we discuss how these might co-exist to regulate skin pigmentation under different conditions, i.e., constitutive and facultative skin pigmentation or physiological and pathological conditions. Moreover, we discuss recent evidence that sheds light on the regulation of melanin exocytosis by melanocytes and internalization by keratinocytes, as well as how melanin is stored within these cells in a compartment that we propose be named the melanokerasome. Finally, we review the state of the art on the molecular mechanisms that lead to melanokerasome positioning above the nuclei of keratinocytes, forming supranuclear caps that shield the nuclear DNA from UV radiation. Thus, we provide a comprehensive overview of the current knowledge on the molecular mechanisms regulating skin pigmentation, from melanin exocytosis by melanocytes and internalization by keratinocytes to processing and polarization within keratinocytes. A better knowledge of these molecular mechanisms will clarify long-lasting questions in the field that are crucial for the understanding of skin pigmentation and can shed light on fundamental aspects of organelle biology. Ultimately, this knowledge can lead to novel therapeutic strategies to treat hypo- or hyper-pigmentation disorders, which have a high socio-economic burden on patients and healthcare systems worldwide, as well as cosmetic applications.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent2458370
dc.identifier.doi10.3390/ijms241411289
dc.identifier.issn1422-0067
dc.identifier.otherPURE: 66779741
dc.identifier.otherPURE UUID: b1c8dfe2-45db-4f0e-a9c3-2a46d229104e
dc.identifier.otherORCID: /0000-0001-8867-2407/work/138445712
dc.identifier.otherScopus: 85165987821
dc.identifier.otherPubMed: 37511054
dc.identifier.otherORCID: /0000-0001-8867-2407/work/135613032
dc.identifier.urihttp://hdl.handle.net/10362/155909
dc.identifier.urlhttps://doi.org/10.3390/ijms241411289
dc.language.isoeng
dc.peerreviewedyes
dc.subjectkeratinocyte
dc.subjectmelanin
dc.subjectmelanin polarization
dc.subjectmelanin processing
dc.subjectmelanin transfer
dc.subjectmelanocore
dc.subjectmelanocyte
dc.subjectmelanokerasome
dc.subjectmelanosome
dc.titleMelanin’s Journey from Melanocytes to Keratinocytes: Uncovering the Molecular Mechanisms of Melanin Transfer and Processingen
dc.typejournal article
degois.publication.issue14
degois.publication.titleInternational Journal of Molecular Sciences
degois.publication.volume24
dspace.entity.typePublication
person.familyNameCabaço
person.familyNameSeabra
person.familyNameBarral
person.givenNameLuís C.
person.givenNameMiguel
person.givenNameDuarte
person.identifier1756697
person.identifier.ciencia-id6D1D-EC36-6BA3
person.identifier.ciencia-id2512-FAEF-E26F
person.identifier.ciencia-id8810-DEBC-025E
person.identifier.orcid0000-0003-0976-1781
person.identifier.orcid0000-0002-6404-4892
person.identifier.orcid0000-0001-8867-2407
person.identifier.ridM-3280-2013
person.identifier.ridE-7548-2013
person.identifier.scopus-author-id57224771399
person.identifier.scopus-author-id7004369652
person.identifier.scopus-author-id6602513159
rcaap.rightsopenAccess
relation.isAuthorOfPublicationb545a125-c8cb-43af-a0c2-8b4dd1f7ee5f
relation.isAuthorOfPublicationd6eeb095-df2d-4fd0-8241-ab826e5ecb1d
relation.isAuthorOfPublicatione8205a0a-7fb2-450a-9917-417ec75d88b3
relation.isAuthorOfPublication.latestForDiscoveryb545a125-c8cb-43af-a0c2-8b4dd1f7ee5f

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