Endocytosis of GluN2B-containing NMDA receptors mediates NMDA-induced excitotoxicity.
Mol Pain
; 13: 1744806917701921, 2017 01.
Article
em En
| MEDLINE
| ID: mdl-28326942
ABSTRACT
Abstract N-methyl-D-aspartate (NMDA) receptor overactivation is involved in neuronal damage after stroke. However, the mechanism underlying NMDA receptor-mediated excitotoxicity remains unclear. In this study, we confirmed that excessive activation of NMDARs led to cell apoptosis in PC12 cells and in primary cultured cortical neurons, which was mediated predominantly by the GluN2B-containing, but not the GluN2A-containing NMDARs. In addition, Clathrin-dependent endocytosis participated in NMDA-induced excitotoxicity. Furthermore, we identified that GluN2B-containing NMDARs underwent endocytosis during excessive NMDA treatment. Peptides specifically disrupting the interaction between GluN2B and AP-2 complex not only blocked endocytosis of GluN2B induced by NMDA treatment but also abolished NMDA-induced excitotoxicity. These results demonstrate that Clathrin-dependent endocytosis of GluN2B-containing NMDARs is critical to NMDA-induced excitotoxicity in PC12 cells and in primary cultured cortical neurons, and therefore provide a novel target for blocking NMDAR-mediated excitotoxicity.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de N-Metil-D-Aspartato
/
Endocitose
Limite:
Animals
Idioma:
En
Revista:
Mol Pain
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
/
PSICOFISIOLOGIA
Ano de publicação:
2017
Tipo de documento:
Article