• Furong Cheng, Xin Li, Yaohua Li, Chaodong Wang, Tao Wang, Guangwei Liu, Andrius Baskys, Kenji Uéda, Piu Chan, and Shun Yu.
• Department of Neurobiology and the Sino-Japan Joint Laboratory on Neurodegenerative Diseases, Key Laboratory of Neurodegenerative Diseases (Capital Medical University), Ministry of Education, Xuanwu Hospital of China Capital Medical University, Beijing, China.
• J. Neurochem. 2011 Nov 1;119(4):815-25.

AbstractAbnormalities 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 Ca(2+) 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.© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

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