Caveolin-1-mediated internalization of the vitamin C transporter SVCT2 in microglia triggers an inflammatory phenotype - PubMed (original) (raw)
. 2017 Mar 28;10(472):eaal2005.
doi: 10.1126/scisignal.aal2005.
Renato Socodato 2, Teresa Canedo 2, Cátia M Silva 2, Tânia Martins 3 4, Vivian S M Coreixas 3 5, Erick C Loiola 3 5, Burkhard Gess 6 7, Dominik Röhr 6, Ana R Santiago 3 4, Peter Young 6, Richard D Minshall 8, Roberto Paes-de-Carvalho 5, António F Ambrósio 3 4, João B Relvas 1
Affiliations
- PMID: 28351945
- DOI: 10.1126/scisignal.aal2005
Caveolin-1-mediated internalization of the vitamin C transporter SVCT2 in microglia triggers an inflammatory phenotype
Camila C Portugal et al. Sci Signal. 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.
Copyright © 2017, American Association for the Advancement of Science.
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