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- Title
α-Synuclein promotes clathrin-mediated NMDA receptor endocytosis and attenuates NMDA-induced dopaminergic cell death.
- Authors
Cheng, Furong; Li, Xin; Li, Yaohua; Wang, Chaodong; Wang, Tao; Liu, Guangwei; Baskys, Andrius; Uéda, Kenji; Chan, Piu; Yu, Shun
- Abstract
J. Neurochem. (2011) 119, 815-825. Abstract Abnormalities of α-synuclein (α-syn) and NMDA receptors (NMDARs) are implicated in the pathogenesis of Parkinson's disease. However, how these proteins interact with each other has not been elucidated. Here, the effect of α-syn on NMDARs was investigated by examining the alterations of surface NMDAR NR1 subunits in MES23.5 dopaminergic cells transfected with the human α-syn gene as well as in cells treated with extracellularly added human α-syn. As demonstrated previously that α-syn can enter cells in a non-endocytic manner without being degraded by the cellular proteolytic systems, the extracellularly added α-syn entered the cytoplasm of MES23.5 cells in a concentration-dependent manner. Both the α-syn-transfected cells and α-syn-treated cells exhibited increased intracellular α-syn levels and reduced surface NR1 without altering the total NR1. The α-syn-induced surface NR1 reduction was accompanied by suppression of NMDA-elicited intracellular Ca2+ elevation and reductions of NMDA-induced caspase 3 activation and cell death, which was abolished by hypotonic shock and K+ depletion, a procedure that blocks clathrin-mediated endocytosis, and by suppression of RAB5B expression with anti-RAB5B oligonucleotides. The data obtained provide evidence for the first time that α-syn may promote clathrin-mediated NMDAR endocytosis.
- Subjects
METHYL aspartate; PARKINSON'S disease; ENDOCYTOSIS; OLIGONUCLEOTIDES; PROTEOLYTIC enzyme genes; CELL death
- Publication
Journal of Neurochemistry, 2011, Vol 119, Issue 4, p815
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2011.07460.x