来自美国立卫生研究院国家神经疾病和中风研究院(the National Institute of Neurological Disorders and Stroke),上海交通大学医学院神经学系等处的研究人员在之前研究的基础上,发现了三种SNARE结合蛋白之一:Snapin的两个重要作用,这对于研究突触小泡融合,以及融合同步化具有重要意义。这一研究成果公布在Neuron杂志上。
领导这一研究的是美国立卫生研究院的盛祖杭教授,其1987年于上海第二医科大学获医学硕士学位,2000年被聘为上海第二医科大学神经生物学教研室客座教授,2001年被聘为二医大长江讲座教授,二医大与美国NIH联合培养研究生计划的主要策划者和主持人。
研究人员从Snapin缺陷突变小鼠上分离得到皮层神经细胞,发现Snapin能有助于突触小泡(Synaptic vesicle,SV)的同时释放。而且Snapin缺陷也会导致EPSCs出现多个peak,衰减和裂变时间增加,出现无法同步的SV融合。
另外研究人员还发现Snapin-C66A(SNAP-25和Synaptotagmin二聚体缺陷)的表达会减小RRP的大小,但对同步融合的影响比较小,这些研究成果说明Snain具有双重作用:增强SV的功能,以及调节同步SV融合。(生物谷Bioon.com)
生物谷推荐原始出处:
Neuron, Volume 61, Issue 3, 412-424, 12 February 2009 doi:10.1016/j.neuron.2008.12.029
Snapin Facilitates the Synchronization of Synaptic Vesicle Fusion
Ping-Yue Pan1,2,Jin-Hua Tian1andZu-Hang Sheng1,,
1 Synaptic Function Section, The Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 35, Room 3B203, 35 Convent Drive, Bethesda, MD 20892-3701, USA
2 Department of Neurobiology, School of Medicine, Shanghai Jiaotong University, Shanghai 200025, China
Summary
Synaptic vesicle (SV) fusion is a fine-tuned process requiring a concert of fusion machineries. Using cortical neurons from snapin-deficient mice, we reveal a role for Snapin in facilitating synchronous release. In addition to reduced frequency of miniature excitatory postsynaptic currents (mini-EPSCs) and smaller release-ready vesicle pool (RRP) size, snapin deficiency results in EPSCs with multiple peaks and increased rise and decay times, reflecting desynchronized SV fusion. These defects impair both synaptic precision and efficacy during sustained neurotransmission. Transient expression of Snapin not only rescues the slowed kinetics of EPSCs, but also further accelerates the rate found in wild-type neurons. Furthermore, expression of Snapin-C66A, a dimerization-defective mutant with impaired interactions with SNAP-25 and Synaptotagmin, reduces the RRP size but exhibits less effect on synchronized fusion. Our studies provide mechanistic insights into a dual role of Snapin in enhancing the efficacy of SV priming and in fine-tuning synchronous SV fusion.