Functional interaction of synapsin and Rab3a in the presynaptic vesicle cycle

许多神经系统疾病是由于神经细胞之间的交流中断而引起的。神经元通过从神经末梢释放神经递质进行交流。递质释放受损可能导致某些形式的癫痫。传递分子被包裹在突触囊泡中，囊泡的释放是由许多蛋白质调节的。突触蛋白是最丰富的突触囊泡蛋白，其缺乏导致癫痫发作。过去的研究表明，消除另一种囊泡蛋白Rab3a可以挽救由突触蛋白缺失引起的癫痫。该项目将研究这两种蛋白质如何在神经末梢内相互作用。为此，将对缺乏突触素、Rab3a或两种蛋白质的基因工程小鼠进行研究。高分辨率显微镜观察囊泡动力学，电记录监测神经元活动。此外，将开发神经末梢的计算模型，以测试蛋白质相互作用的假设是否正确预测突触素和Rab3a如何影响递质的释放。我们的研究结果将阐明突触素依赖性癫痫的机制，并为其治疗提供新的策略。中加勒比大学（UCC）是一所西班牙裔服务机构，致力于为波多黎各学生提供一流的教育和科学培训。本项目为优秀的培训计划奠定了基础。实验将由研究生、本科生和医学生进行，因此该项目将为学生的职业生涯提供支持。该项目涉及UCC和韦恩州立大学之间的合作，这为波多黎各学生在研究密集型机构中进行实践创造了有利的机会。因此，该项目将整合研究和培训，促进波多黎各学生的职业发展，并有助于促进劳动力多样性。

Numerous neurological disorders result from disruptions in the communication between nerve cells. Neurons communicate by releasing neuronal transmitters from nerve endings. Impaired transmitter release may produce certain forms of epilepsy. Transmitter molecules are packed into synaptic vesicles, and the preparation of vesicles for release is regulated by numerous proteins. Synapsin is the most abundant synaptic vesicle protein, and its deficiency causes epileptic seizures. Past work shows elimination of another vesicle protein, Rab3a, rescues epilepsy caused by synapsin deletion. This project will investigate how these two proteins interact within nerve endings. To do this, genetically engineered mice that lack synapsin, Rab3a, or both proteins, will be studied. High resolution microscopy to observe vesicle dynamics, and electrical recording will be performed to monitor neuronal activity. In addition, a computational model of the nerve ending will be developed to test whether hypotheses of the protein interaction correctly predict how synapsin and Rab3a affect the release of transmitters. The results of our study will elucidate the mechanisms of synapsin-dependent epilepsy and will suggest new strategies for its treatment. The Universidad Central del Caribe (UCC) is a Hispanic serving institution which strives to provide Puerto Rican students with first-rate education and scientific training. The present project creates a foundation for an excellent training program. The experiments will be performed by graduate, undergraduate, and medical students, and thus the project will provide a support for the students' careers. The project involves collaboration between the UCC and the Wayne State University, and this creates advantageous opportunities for Puerto Rico students to have a practice in a research intense institution. Thus, this project will integrate research and training, advance careers of Puerto Rico students, and help to promote workforce diversity.