Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/110355
Author(s): 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
Title: Caveolin-1-mediated internalization of the vitamin C transporter SVCT2 in microglia triggers an inflammatory phenotype
Publisher: American Association for the Advancement of Science
Issue Date: 2017
Abstract: 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.
Subject: 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
URI: http://hdl.handle.net/10216/110355
Source: Science Signaling, vol. 10(472), pii: eaal2005
Related Information: info:eu-repo/grantAgreement/FCT/COMPETE/119937/PT
info:eu-repo/grantAgreement/FCT/5876-PPCDTI/125980/PT
info:eu-repo/grantAgreement/FCT/5876/147358/PT
info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F91962%2F2012/PT
info:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F91833%2F2012/PT
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
Appears in Collections:I3S - Artigo em Revista Científica Internacional

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