CAREER: Molecular and Genetic Analysis of Synaptic Vesicle Recycling

神经系统的认知功能在很大程度上取决于神经元通讯的完整性。这一过程包括突触囊泡释放神经递质、激活突触后受体和突触囊泡再循环。 回收步骤对于连续的突触传递至关重要。 然而，我们对囊泡回收及其调节的理解仍然是初步的。 张博士将利用遗传学、分子生物学和果蝇电生理学的力量来研究囊泡回收的分子机制。 最近，Zhang博士和他的同事们发现，网格蛋白介导的内吞作用是一种主要的囊泡回收途径，受到哺乳动物网格蛋白组装蛋白AP 180的推定果蝇同源物AP 180（如AP 180）的严格调控。 Zhang博士将测试β-淀粉样蛋白是否是AP 180的功能同源物，并精确确定β-淀粉样蛋白如何调节囊泡重组。 他还将确定网格蛋白外壳组装的关键结构基序，并确定它们在突触传递中的作用。这些研究的结果具有广泛的生物学和临床意义，因为网格蛋白通常用于内吞作用和细胞内蛋白运输。张博士的研究也与学生的培训和当地学校的推广紧密结合。 他将为他的大学的本科生和研究生开发新的课程。 他还将扩大一个正在进行的年度研讨会，以熟悉当地小学和高中学生和他们的教师与基本的神经生物学研究。 通过这些教育和推广工作，张博士希望激励更多的年轻学生从事生物研究和教育事业。 这个CAREER奖不仅将促进我们对突触传递的理解，而且还有助于开发有利于未来神经生物学家的项目。

IBN-0093170ZHANGCognitive functions of the nervous system depend largely on the integrity of neuronal communication. This process includes the release of neurotransmitter from synaptic vesicles, activation of postsynaptic receptors, and recycling of synaptic vesicles. The recycling step is crucial for continuous synaptic transmission. However, our understanding of vesicle recycling and its regulation remains rudimentary. Dr. Zhang will exploit the power of genetics, molecular biology, and electrophysiology in the fruitfly Drosophila to investigate the molecular mechanisms underlying vesicle recycling. Recently, Dr. Zhang and his colleagues revealed that clathrin-mediated endocytosis, a major vesicle recycling pathway, is tightly regulated by LAP (like-AP180), a putative fly homolog of the mammalian clathrin assembly protein AP180. Dr. Zhang will test whether LAP is a functional homolog of AP180 and determine precisely how LAP regulates vesicle reformation. He will also identify structural motifs critical for clathrin coat assembly and determine their roles in synaptic transmission. The results from these studies have broad biological and clinical significance because clathrin is commonly used for endocytosis and intracellular protein trafficking. Dr. Zhang's research is also closely integrated with training of students and outreach to local schools. He will develop new curriculum for both undergraduates and graduates at his University. He will also expand an on-going annual workshop to familiarize local elementary and high students and their teachers with basic neurobiological research. Through these education and outreach efforts, Dr. Zhang hopes to inspire more young students to pursue careers in biological research and education. This CAREER award will not only advance our understanding of synaptic transmission, but also help develop programs benefiting future neurobiologists.