Genetic and Proteomic Analysis of Protein Sorting and Retrieval During Synaptic Vesicle Endocytosis

突触小泡胞吞过程中蛋白质分选和检索的遗传和蛋白质组学分析

• 批准号: 0822236
• 负责人: Bing Zhang
• 金额: $ 54万
• 依托单位: University of Oklahoma Norman Campus
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0822236&HistoricalAwards=false
• 关键词: Genetic; Proteomic; Analysis; Protein; Sorting

A unique feature of the nervous system is the vast number of cell-cell connections called synapses. At synapses, nerve cells communicate with each other and with other target cells. At chemical synapses, and upon activation, nerve cells release transmitter from small synaptic vesicles (SVs) and then recycle these vesicles for reuse. Hence, SV recycling plays a major role in neuronal function. Clathrin and its associated molecules are critical players in vesicle recycling. However, the molecular mechanisms by which SVs are recycled are not fully understood. This project is directed towards understanding how SV proteins are recruited and recycled into newly formed vesicles. Genetic and biochemical studies from Dr. Zhang's laboratory and others suggest that the clathrin-accessory protein AP180 regulates both the rate and the fidelity of clathrin-mediated recycling of SVs. This project will test the hypothesis that AP180 also plays a role in helping retrieve vesicle proteins during vesicle recycling. They will be examining whether and how the composition of SVs is altered in mutant fruit flies (Drosophila) deficient of AP180 and also will investigate the mode by which AP180 might interact with vesicular proteins. These studies are expected to advance the understanding of SV recycling and nerve cell function. This project also closely integrates research with education, training, and outreach to local communities. He has trained and mentored undergraduates, graduates, and postdoctoral fellows, including women and students from underrepresented groups. Eleven undergraduates were co-authors with him on a prior NSF-sponsored project, including one as first author. During this funding period, he will continue his educational efforts in student mentoring and course development. In addition, he will be reach out to local schools and train elementary science teachers through a summer program organized by the Sam Noble Oklahoma Museum of Natural History at OU.

神经系统的一个独特特征是大量的细胞间连接，称为突触。在突触处，神经细胞相互通信，也与其他靶细胞通信。在化学突触，一旦激活，神经细胞从小突触小泡(SVS)释放递质，然后回收这些小泡重复使用。因此，SV循环在神经元功能中起着重要作用。笼状蛋白及其相关分子在囊泡循环中起着关键作用。然而，SVS循环的分子机制还不完全清楚。这个项目旨在了解SV蛋白是如何被招募并循环进入新形成的囊泡的。张博士的实验室和其他人的遗传和生化研究表明，网状蛋白辅助蛋白AP180调节网状蛋白介导的SVS循环的速度和保真度。该项目将验证AP180在囊泡循环过程中也起到帮助回收囊泡蛋白质的作用的假设。他们将研究缺乏AP180的突变果蝇(果蝇)是否以及如何改变SVS的组成，并将研究AP180可能与囊泡蛋白相互作用的方式。这些研究有望促进对SV循环和神经细胞功能的理解。该项目还将研究与教育、培训和对当地社区的宣传紧密结合起来。他曾培训和指导本科生、毕业生和博士后研究员，包括来自代表性不足群体的妇女和学生。11名本科生与他共同撰写了之前由NSF赞助的一个项目，其中一人是第一作者。在此资助期间，他将继续在学生辅导和课程开发方面的教育努力。此外，他还将接触当地学校，并通过俄亥俄州立大学萨姆·诺布尔自然历史博物馆组织的暑期项目培训初级科学教师。