VPS10P domain receptors emerge as central regulators of intracellular protein sorting in neurons with relevance for various brain pathologies. Here, we identified a role for the family member SorCS2 in protection of neurons from oxidative stress and epilepsy-induced cell death. We show that SorCS2 acts as sorting receptor that sustains cell surface expression of the neuronal amino acid transporter EAAT3 to facilitate import of cysteine, required for synthesis of the reactive oxygen species scavenger glutathione. Lack of SorCS2 causes depletion of EAAT3 from the plasma membrane and impairs neuronal cysteine uptake. As a consequence, SorCS2-deficient mice exhibit oxidative brain damage that coincides with enhanced neuronal cell death and increased mortality during epilepsy. Our findings highlight a protective role for SorCS2 in neuronal stress response and provide a possible explanation for upregulation of this receptor seen in surviving neurons of the human epileptic brain.
Pubmed ID: 30840898 RIS Download
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View all literature mentionslaboratory mouse with name C57BL/6N from MGI.
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View all literature mentionsThis monoclonal targets Glutathione: N-ethylmaleimide adduct clone 8.1GSH
View all literature mentionsThis polyclonal targets Mouse SorCS2
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View all literature mentionsThis unknown targets Metabotropic Glutamate Receptor 2/3
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View all literature mentionsThis monoclonal targets Glial Fibrillary Acidic Protein (GFAP)
View all literature mentionsThis polyclonal targets GFP : Trial Size
View all literature mentionsThis monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204)
View all literature mentionsThis polyclonal targets Mouse Addicsin
View all literature mentionsThis monoclonal targets Glutathione: N-ethylmaleimide adduct clone 8.1GSH
View all literature mentionsThis monoclonal targets Mouse GluR2 Clone L21/32
View all literature mentionsThis polyclonal targets Mouse SorCS2
View all literature mentionsThis monoclonal targets Synaptophysin 1
View all literature mentionsThis polyclonal targets Mouse SorCS2
View all literature mentionsThis monoclonal targets Rab11
View all literature mentionsThis monoclonal targets Rab7
View all literature mentionsThis monoclonal targets PSD95
View all literature mentionsThis unknown targets Metabotropic Glutamate Receptor 2/3
View all literature mentionsThis polyclonal targets Mouse Addicsin
View all literature mentionsThis monoclonal targets Glutathione: N-ethylmaleimide adduct clone 8.1GSH
View all literature mentionsThis monoclonal targets Mouse GluR2 Clone L21/32
View all literature mentionsThis monoclonal targets Glial Fibrillary Acidic Protein (GFAP)
View all literature mentionsThis polyclonal targets GFP : Trial Size
View all literature mentionsThis monoclonal targets Phospho-p44/42 MAPK (Erk1/2) (Thr202/Tyr204)
View all literature mentionsThis polyclonal targets RCJMB04_4h19
View all literature mentions