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Melanin transferred to keratinocytes resides in non-degradative endocytic compartments

2018-03Artigo científico Acesso aberto
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dc.contributor.authorCorreia, Maria S
dc.contributor.authorMoreiras, Hugo
dc.contributor.authorPereira, Francisco J C
dc.contributor.authorNeto, Matilde V
dc.contributor.authorFestas, Tiago C
dc.contributor.authorTarafder, Abul K
dc.contributor.authorRamalho, José S
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.institutionCentro de Estudos de Doenças Crónicas (CEDOC)
dc.contributor.pblElsevier
dc.date.accessioned2023-02-16T22:13:43Z
dc.date.available2023-02-16T22:13:43Z
dc.date.issued2018-03
dc.descriptionFunding: We thank the staff from the Unit of Imaging and Cytometry of the Instituto Gulbenkian de Ciência for assistance in microscopy and flow cytometry protocol adjustments, the CEDOC Microscopy Facility for assistance in image acquisition and analysis, Dot Bennett for the kind gift of cell lines, and Alistair Hume for the kind gift of anti-Rab5 antibody. This project was supported by Fundação para a Ciência e a Tecnologia (FCT), Portugal (PTDC/BIA-BCM/ 111735/2009, EXPL/BEX-BCM/0379/2013), MSC and HM were supported by FCT PhD studentships (SFRH/BD/65381/2009 and PD/BD/114118/2015, respectively), FJCP was supported by an FCT postdoctoral fellowship (SFRH/ BPD/70337/2010), and DCB was supported by the FCT Investigator Program (IF/00501/2014/CP1252/CT0001).
dc.description.abstractMelanin 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.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent10
dc.format.extent2593218
dc.identifier.doi10.1016/j.jid.2017.09.042
dc.identifier.issn0022-202X
dc.identifier.otherPURE: 3278434
dc.identifier.otherPURE UUID: 785ab1ef-058f-4d6e-99bd-ff19999aa566
dc.identifier.otherPubMed: 29074272
dc.identifier.otherScopus: 85042509194
dc.identifier.otherWOS: 000425749900035
dc.identifier.otherORCID: /0000-0001-8867-2407/work/123561651
dc.identifier.urihttp://hdl.handle.net/10362/149314
dc.language.isoeng
dc.peerreviewedyes
dc.subjectLAMP
dc.subjectlysosomal-associated membrane protein
dc.subjectPAR
dc.subjectPBS
dc.subjectphosphate buffered saline
dc.subjectprotease-activated receptor
dc.subjectsiRNA
dc.subjectsmall interfering RNA
dc.titleMelanin transferred to keratinocytes resides in non-degradative endocytic compartmentsen
dc.typejournal article
degois.publication.firstPage637
degois.publication.issue3
degois.publication.lastPage646
degois.publication.titleJournal Of Investigative Dermatology
degois.publication.volume138
dspace.entity.typePublication
person.familyNameSeabra
person.familyNameBarral
person.givenNameMiguel
person.givenNameDuarte
person.identifier.ciencia-id2512-FAEF-E26F
person.identifier.ciencia-id8810-DEBC-025E
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-id7004369652
person.identifier.scopus-author-id6602513159
rcaap.rightsopenAccess
relation.isAuthorOfPublicationd6eeb095-df2d-4fd0-8241-ab826e5ecb1d
relation.isAuthorOfPublicatione8205a0a-7fb2-450a-9917-417ec75d88b3
relation.isAuthorOfPublication.latestForDiscoveryd6eeb095-df2d-4fd0-8241-ab826e5ecb1d

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