机构：[1]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神经变性病教育部重点实验室首都医科大学宣武医院[2]UCLA-Kern Psychiatry Residency Program, Kern Medical Center & Kern County Mental Health, David Geffen School of Medicine at UCLA, Bakersfield, California, USA[3]Division of Psychobiology, Tokyo Institute of Psychiatry, Tokyo, Japan
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 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 alpha-syn may promote clathrin-mediated NMDAR endocytosis.
基金：
National High Technology Research and Development Program (‘‘863’’ Program) of China (2006AA02A408), National Basic Research Program (‘‘973’’ Program) of China (2011CB504101),
National Natural Science Foundation of China (30270482, 30271437, 30430280, and 81071014), Natural Science Foundation of Beijing (7022011 and 7102076),
and Funding Project for Academic Human Resources Development in the Institutions of Higher Learning under the Jurisdiction of Beijing Municipality (PHR200907113).
第一作者机构：[1]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
通讯作者：
通讯机构：[*]Department of Neurobiology, Beijing Institute of Geriatrics, Xuanwu Hospital of China Capital Medical University, No. 45 Changchun Street, Beijing 100053, China
推荐引用方式(GB/T 7714)：
Furong Cheng,Xin Li,Yaohua Li,et al.alpha-Synuclein promotes clathrin-mediated NMDA receptor endocytosis and attenuates NMDA-induced dopaminergic cell death[J].JOURNAL OF NEUROCHEMISTRY.2011,119(4):815-825.doi:10.1111/j.1471-4159.2011.07460.x.
APA：
Furong Cheng,Xin Li,Yaohua Li,Chaodong Wang,Tao Wang...&Shun Yu.(2011).alpha-Synuclein promotes clathrin-mediated NMDA receptor endocytosis and attenuates NMDA-induced dopaminergic cell death.JOURNAL OF NEUROCHEMISTRY,119,(4)
MLA：
Furong Cheng,et al."alpha-Synuclein promotes clathrin-mediated NMDA receptor endocytosis and attenuates NMDA-induced dopaminergic cell death".JOURNAL OF NEUROCHEMISTRY 119..4(2011):815-825
医学