Caveolin-1-mediated internalization of the vitamin C transporter SVCT2 in microglia triggers an inflammatory phenotype

Detalhes bibliográficos
Autor(a) principal: Portugal, CC
Data de Publicação: 2017
Outros Autores: Socodato, R, Canedo, T, Silva, CM, Martins, T, Coreixas, VS, Loiola, EC, Gess, B, Röhr, D, Santiago, AR, Young, P, Minshall, RD, Paes-de-Carvalho, R, Ambrósio, AF, Relvas, JB
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Texto Completo: http://hdl.handle.net/10216/110355
Resumo: Vitamin C is essential for the development and function of the central nervous system (CNS). The plasma membrane sodium-vitamin C cotransporter 2 (SVCT2) is the primary mediator of vitamin C uptake in neurons. SVCT2 specifically transports ascorbate, the reduced form of vitamin C, which acts as a reducing agent. We demonstrated that ascorbate uptake through SVCT2 was critical for the homeostasis of microglia, the resident myeloid cells of the CNS that are essential for proper functioning of the nervous tissue. We found that depletion of SVCT2 from the plasma membrane triggered a proinflammatory phenotype in microglia and resulted in microglia activation. Src-mediated phosphorylation of caveolin-1 on Tyr14 in microglia induced the internalization of SVCT2. Ascorbate treatment, SVCT2 overexpression, or blocking SVCT2 internalization prevented the activation of microglia. Overall, our work demonstrates the importance of the ascorbate transport system for microglial homeostasis and hints that dysregulation of ascorbate transport might play a role in neurological disorders.
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spelling Caveolin-1-mediated internalization of the vitamin C transporter SVCT2 in microglia triggers an inflammatory phenotypeAnimalsAscorbic Acid/metabolismBlotting, WesternCaveolin 1/metabolismCell LineCell Membrane/metabolismCytokines/metabolismEndocytosisFemaleHEK293 CellsHumansInflammation Mediators/metabolismMaleMice KnockoutMicroglia/cytologyMicroglia/metabolism,Microscopy ConfocalNeurons/metabolismPhosphorylationRats, WistarSodium-Coupled Vitamin C Transporters/geneticsSodium-Coupled Vitamin C Transporters/metabolismVitamin C is essential for the development and function of the central nervous system (CNS). The plasma membrane sodium-vitamin C cotransporter 2 (SVCT2) is the primary mediator of vitamin C uptake in neurons. SVCT2 specifically transports ascorbate, the reduced form of vitamin C, which acts as a reducing agent. We demonstrated that ascorbate uptake through SVCT2 was critical for the homeostasis of microglia, the resident myeloid cells of the CNS that are essential for proper functioning of the nervous tissue. We found that depletion of SVCT2 from the plasma membrane triggered a proinflammatory phenotype in microglia and resulted in microglia activation. Src-mediated phosphorylation of caveolin-1 on Tyr14 in microglia induced the internalization of SVCT2. Ascorbate treatment, SVCT2 overexpression, or blocking SVCT2 internalization prevented the activation of microglia. Overall, our work demonstrates the importance of the ascorbate transport system for microglial homeostasis and hints that dysregulation of ascorbate transport might play a role in neurological disorders.American Association for the Advancement of Science20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/pdfhttp://hdl.handle.net/10216/110355eng1945-087710.1126/scisignal.aal2005Portugal, CCSocodato, RCanedo, TSilva, CMMartins, TCoreixas, VSLoiola, ECGess, BRöhr, DSantiago, ARYoung, PMinshall, RDPaes-de-Carvalho, RAmbrósio, AFRelvas, JBinfo:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2025-02-27T17:25:30Zoai:repositorio-aberto.up.pt:10216/110355Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T22:13:49.018990Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
dc.title.none.fl_str_mv Caveolin-1-mediated internalization of the vitamin C transporter SVCT2 in microglia triggers an inflammatory phenotype
title Caveolin-1-mediated internalization of the vitamin C transporter SVCT2 in microglia triggers an inflammatory phenotype
spellingShingle Caveolin-1-mediated internalization of the vitamin C transporter SVCT2 in microglia triggers an inflammatory phenotype
Portugal, CC
Animals
Ascorbic Acid/metabolism
Blotting, Western
Caveolin 1/metabolism
Cell Line
Cell Membrane/metabolism
Cytokines/metabolism
Endocytosis
Female
HEK293 Cells
Humans
Inflammation Mediators/metabolism
Male
Mice Knockout
Microglia/cytology
Microglia/metabolism,Microscopy Confocal
Neurons/metabolism
Phosphorylation
Rats, Wistar
Sodium-Coupled Vitamin C Transporters/genetics
Sodium-Coupled Vitamin C Transporters/metabolism
title_short Caveolin-1-mediated internalization of the vitamin C transporter SVCT2 in microglia triggers an inflammatory phenotype
title_full Caveolin-1-mediated internalization of the vitamin C transporter SVCT2 in microglia triggers an inflammatory phenotype
title_fullStr Caveolin-1-mediated internalization of the vitamin C transporter SVCT2 in microglia triggers an inflammatory phenotype
title_full_unstemmed Caveolin-1-mediated internalization of the vitamin C transporter SVCT2 in microglia triggers an inflammatory phenotype
title_sort Caveolin-1-mediated internalization of the vitamin C transporter SVCT2 in microglia triggers an inflammatory phenotype
author Portugal, CC
author_facet Portugal, CC
Socodato, R
Canedo, T
Silva, CM
Martins, T
Coreixas, VS
Loiola, EC
Gess, B
Röhr, D
Santiago, AR
Young, P
Minshall, RD
Paes-de-Carvalho, R
Ambrósio, AF
Relvas, JB
author_role author
author2 Socodato, R
Canedo, T
Silva, CM
Martins, T
Coreixas, VS
Loiola, EC
Gess, B
Röhr, D
Santiago, AR
Young, P
Minshall, RD
Paes-de-Carvalho, R
Ambrósio, AF
Relvas, JB
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Portugal, CC
Socodato, R
Canedo, T
Silva, CM
Martins, T
Coreixas, VS
Loiola, EC
Gess, B
Röhr, D
Santiago, AR
Young, P
Minshall, RD
Paes-de-Carvalho, R
Ambrósio, AF
Relvas, JB
dc.subject.por.fl_str_mv Animals
Ascorbic Acid/metabolism
Blotting, Western
Caveolin 1/metabolism
Cell Line
Cell Membrane/metabolism
Cytokines/metabolism
Endocytosis
Female
HEK293 Cells
Humans
Inflammation Mediators/metabolism
Male
Mice Knockout
Microglia/cytology
Microglia/metabolism,Microscopy Confocal
Neurons/metabolism
Phosphorylation
Rats, Wistar
Sodium-Coupled Vitamin C Transporters/genetics
Sodium-Coupled Vitamin C Transporters/metabolism
topic Animals
Ascorbic Acid/metabolism
Blotting, Western
Caveolin 1/metabolism
Cell Line
Cell Membrane/metabolism
Cytokines/metabolism
Endocytosis
Female
HEK293 Cells
Humans
Inflammation Mediators/metabolism
Male
Mice Knockout
Microglia/cytology
Microglia/metabolism,Microscopy Confocal
Neurons/metabolism
Phosphorylation
Rats, Wistar
Sodium-Coupled Vitamin C Transporters/genetics
Sodium-Coupled Vitamin C Transporters/metabolism
description Vitamin C is essential for the development and function of the central nervous system (CNS). The plasma membrane sodium-vitamin C cotransporter 2 (SVCT2) is the primary mediator of vitamin C uptake in neurons. SVCT2 specifically transports ascorbate, the reduced form of vitamin C, which acts as a reducing agent. We demonstrated that ascorbate uptake through SVCT2 was critical for the homeostasis of microglia, the resident myeloid cells of the CNS that are essential for proper functioning of the nervous tissue. We found that depletion of SVCT2 from the plasma membrane triggered a proinflammatory phenotype in microglia and resulted in microglia activation. Src-mediated phosphorylation of caveolin-1 on Tyr14 in microglia induced the internalization of SVCT2. Ascorbate treatment, SVCT2 overexpression, or blocking SVCT2 internalization prevented the activation of microglia. Overall, our work demonstrates the importance of the ascorbate transport system for microglial homeostasis and hints that dysregulation of ascorbate transport might play a role in neurological disorders.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-01-01T00:00:00Z
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/10216/110355
url http://hdl.handle.net/10216/110355
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1945-0877
10.1126/scisignal.aal2005
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Association for the Advancement of Science
publisher.none.fl_str_mv American Association for the Advancement of Science
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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