期刊
SCIENCE SIGNALING
卷 10, 期 472, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.aal2005
关键词
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资金
- FEDER
- FCT, Portugal [Norte-01-0145-FEDER-000008000008, PTDC/NEU-OSD/1113/2012, PEst-C/SAU/UI3282/2011-2013, UID/NEU/04539/2013]
- Norte Portugal Regional Operational Programme), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund [FCOMP-01-0124FEDER-021333, PTDC/SAU-NMC/119937/2010]
- Centro 2020 Regional Operational Programme [CENTRO-01-0145FEDER-000008]
- FCT [FRH/BPD/91962/2012, SFRH/BPD/91833/2012]
- Fundação para a Ciência e a Tecnologia [PTDC/NEU-OSD/1113/2012, PTDC/SAU-NMC/119937/2010, UID/NEU/04539/2013] Funding Source: FCT
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 Tyr(14) 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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