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

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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.