α-Synuclein promotes clathrin-mediated NMDA receptor endocytosis and attenuates NMDA-induced dopaminergic cell death
α-Synuclein promotes clathrin-mediated NMDA receptor endocytosis and attenuates NMDA-induced dopaminergic cell death
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DOI：
10.1111/j.1471-4159.2011.07460.x
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发表时间：
2011-11-01
影响因子：
4.7
通讯作者：
Yu, Shun
中科院分区：
文献类型：
--
作者：
Cheng, Furong;Li, Xin;Yu, Shun
Abnormalities of alpha-synuclein (alpha-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 alpha-syn on NMDARs was investigated by examining the alterations of surface NMDAR NR1 subunits in MES23.5 dopaminergic cells transfected with the human alpha-syn gene as well as in cells treated with extracellularly added human alpha-syn. As demonstrated previously that alpha-syn can enter cells in a non-endocytic manner without being degraded by the cellular proteolytic systems, the extracellularly added alpha-syn entered the cytoplasm of MES23.5 cells in a concentration-dependent manner. Both the alpha-syn-transfected cells and alpha-syn-treated cells exhibited increased intracellular alpha-syn levels and reduced surface NR1 without altering the total NR1. The alpha-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 alpha-syn may promote clathrin-mediated NMDAR endocytosis.
