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科技与教学论坛第100期预告

作者: 时间:2018年12月14日 17:15 点击数:

报告题目:Physiological and pathological roles of synaptotagmin-11 in neurons

突触标记蛋白-11在神经元中的生理和病理作用

报告人:王昌河 教授

报告时间:15:00-17:30

报告日期:12月19日

报告地点:雁塔校区 教学一楼303学术报告厅

主办单位:现代教学技术教育部重点实验室、教师专业能力发展中心

报告内容简介:

Loss-of-function mutations in Parkinare the most common causes of autosomal recessive Parkinson’s disease (PD). Many putative substrates of parkin have been reported; their pathogenic roles, however, remain obscure due to poor characterizations particularly in vivo. Here, we show that synaptotagmin-11, encoded by SYT11 and a PD risk gene, is a physiological substrate of parkin and plays a critical role in mediating parkin-linked neurotoxicity. Unilateral overexpression of full-length, but not C2B-truncated, synaptotagmin-11 in the substantia nigra pars compacta (SNpc) impairs ipsilateral striatal dopamine release, causes late-onset degeneration of dopaminergic neurons, and induces progressive contralateral motor abnormalities. Mechanistically, synaptotagmin-11 impairsvesiclepool replenishment and thus dopamine release by inhibiting endocytosis. Furthermore, parkin deficiency induces synaptotagmin-11 accumulation and PD-related neurotoxicity, which is reversedby SYT11 knockdown in the SNpc or dopaminergic neuron-restricted knockout of SYT11. Thus, parkin dysfunction-induced neurotoxicity in PD requires synaptotagmin-11 accumulation in SNpc dopamine neurons. These findings, for the first time, reveal a parkin-synaptotagmin-11 pathogenic pathway and synaptotagmin-11 activity as a novel therapeutic target for PD.

报告人简介:

王昌河,教授,博士生导师,神经科学研究中心主任。西安交通大学青年拔尖人才,陕西省‘百人计划’青年学者,教育部自然科学一等奖获得者(第三完成人)。主要研究方向包括:1)神经分泌与突触传递的调控机制,2)多巴胺系统相关神经疾病(帕金森病、精神分裂症、成瘾、痛)的病理机制。在本领域著名期刊发表相关研究论文26篇,累计影响因子162.6,其中第一/通讯作者论文(SCI)共计13篇(1区TOP期刊7篇),分别发表在Nat Commun (2018,Mov Disord亮点评述),Neuron(2017, Nat Rev Neurosci亮点评述;Faculty1000特别推荐,3次), Sci Signal(2017,封面文章,Science亮点评述),EMBO Rep(2016,封面文章),J Cell Biol (2016,同刊亮点评述),Diabetologia(2015,‘Up front’特别推荐论文),Nat Commun(2014)等期刊上,累计影响因子~90.9(平均影响因子~7.0)。受邀在《中国大百科全书》第三版中负责《胞吐》和《胞吞》两个条目的撰写工作。目前担任中国生物物理学会神经专委员会副主任、秘书长,中国生物物理学会科普委员会委员,中国老年学学会衰老与抗衰老科学委员会委员、CAMPUS Asia Project学术委员会委员,陕西省细胞生物学会理事。