title: Rab11b mediates melanin transfer between donor melanocytes and acceptor keratinocytes via coupled exo/endocytosis.
abstract: The transfer of melanin from melanocytes to keratinocytes is a crucial process underlying maintenance of skin pigmentation and photoprotection against UV damage. Here, we present evidence supporting coupled exocytosis of the melanin core, or melanocore, by melanocytes and subsequent endocytosis by keratinocytes as a predominant mechanism of melanin transfer. Electron microscopy analysis of human skin samples revealed three lines of evidence supporting this: (1) the presence of melanocores in the extracellular space; (2) within keratinocytes, melanin was surrounded by a single membrane; and (3) this membrane lacked the melanosomal membrane protein tyrosinase-related protein 1 (TYRP1). Moreover, co-culture of melanocytes and keratinocytes suggests that melanin exocytosis is specifically induced by keratinocytes. Furthermore, depletion of Rab11b, but not Rab27a, caused a marked decrease in both keratinocyte-stimulated melanin exocytosis and transfer to keratinocytes. Thus, we propose that the predominant mechanism of melanin transfer is keratinocyte-induced exocytosis, mediated by Rab11b through remodeling of the melanosome membrane, followed by subsequent endocytosis by keratinocytes.
authors.affiliation: CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal; Instituto Gulbenkian de Ciência, Oeiras, Portugal; Molecular Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Abul K
authors.initials: AK
authors.lastname: Tarafder
authors.affiliation: Molecular Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Giulia
authors.initials: G
authors.lastname: Bolasco
authors.affiliation: CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal; Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Maria S
authors.initials: MS
authors.lastname: Correia
authors.affiliation: CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal; Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Francisco J C
authors.initials: FJC
authors.lastname: Pereira
authors.affiliation: CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal; Instituto Gulbenkian de Ciência, Oeiras, Portugal.
authors.forename: Lucio
authors.initials: L
authors.lastname: Iannone
authors.affiliation: Molecular Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
authors.forename: Alistair N
authors.initials: AN
authors.lastname: Hume
authors.affiliation: Craniofacial and Orbito-Palpebral Surgery Unit at Chelsea and Westminster Hospital, London, UK.
authors.forename: Niall
authors.initials: N
authors.lastname: Kirkpatrick
authors.affiliation: Laboratorio di Fisiopatologia Cutanea, Istituto Dermatologico San Gallicano, IFO, Rome, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Picardo
authors.affiliation: Laboratorio di Fisiopatologia Cutanea, Istituto Dermatologico San Gallicano, IFO, Rome, Italy; Dipartimento di Medicina Clinica e Molecolare, Azienda Ospedaliera Sant'Andrea, Università di Roma 'La Sapienza', Rome, Italy.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Torrisi
authors.affiliation: CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal.
authors.forename: Inês P
authors.initials: IP
authors.lastname: Rodrigues
authors.affiliation: CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal.
authors.forename: José S
authors.initials: JS
authors.lastname: Ramalho
authors.affiliation: Institute of Ophthalmology, University College London, London, UK.
authors.forename: Clare E
authors.initials: CE
authors.lastname: Futter
authors.affiliation: CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal. Electronic address: duarte.barral@fcm.unl.pt.
authors.forename: Duarte C
authors.initials: DC
authors.lastname: Barral
authors.affiliation: CEDOC, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal; Instituto Gulbenkian de Ciência, Oeiras, Portugal; Molecular Medicine, National Heart and Lung Institute, Imperial College London, London, UK. Electronic address: miguel.seabra@fcm.unl.pt.
authors.forename: Miguel C
authors.initials: MC
authors.lastname: Seabra
mesh_terms: D018920:Coculture Techniques; D004705:Endocytosis; D005089:Exocytosis; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D008543:Melanins / Q000378:metabolism*; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008854:Microscopy, Electron; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D010088:Oxidoreductases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012867:Skin / Q000378:metabolism* / Q000648:ultrastructure; D020691:rab GTP-Binding Proteins / Q000378:metabolism*; D000075745:rab27 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D051907:Lysosomal Membrane Proteins; D008543:Melanins; D008562:Membrane Glycoproteins; D010088:Oxidoreductases; D034741:RNA, Small Interfering; D020691:rab GTP-Binding Proteins; D000075745:rab27 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C489116:LAMP1 protein, human; D052118:Lysosomal-Associated Membrane Protein 1; C489799:TYRP1 protein, human; C066694:RAB27A protein, human