Molecular and Genetic Analysis of Presynaptic Proteins

描述（由申请人提供）：我们的目标是继续对土壤线虫秀丽隐杆线虫中的突触传递进行分子和遗传分析。C.由于线虫的神经系统简单，易于遗传和分子分析，基因组测序完整，因此被用于这些研究。拟议的研究是基于最近的成果和最新的技术进步。三大目标是：（1）深入分析最近描述的rip-1基因，该基因编码一种被认为为突触前神经末梢的组分提供“分子支架”的极大蛋白质;（2）开始研究神经末梢内用于调节包装到每个突触囊泡中的神经递质的量的机制;以及（3）使用C. elegans细胞培养系统，用于体外突触发育和功能的分析。拟议的研究将扩展我们以前的分析突触结构和神经递质功能的土壤线虫秀丽隐杆线虫，并将包括分离的突变体缺乏的调节囊泡内容，并确定特定的分子和信号通路所需的适当调制的量子大小。虽然这是基础研究，但它显然与健康有关，因为适当的神经递质释放对神经系统的正常功能至关重要，而有缺陷的递质释放与许多精神和神经系统疾病有关。

DESCRIPTION (provided by applicant): It is our goal to continue our molecular and genetic analysis of synaptic transmission in the soil nematode Caenorhabditis elegans. C. elegans is being used for these studies because of its simple nervous system, its ease of genetic and molecular analysis, and the complete sequencing of its genome. The proposed research is based on recent results and on recent technological advances. The three broad goals are: (1) to analyze in depth the recently-described rip-1 gene, which encodes an extremely large protein thought to provide a "molecular scaffold" for the components of a presynaptic nerve terminal; (2) to begin an investigation of the mechanisms used within nerve terminals to regulate the amount of neurotransmitter packaged into each synaptic vesicle; and (3) to continue studies using a C. elegans cell culture system for the analysis of synaptic development and function in vitro. The proposed studies will extend our previous analysis of synaptic structure and neurotransmitter function in the soil nematode Caenorhabditis elegans, and will include the isolation of mutants deficient in the regulation of vesicle content, and the identification of specific molecules and signaling pathways required for proper modulation of quantal size. Although this is basic research, it is clearly relevant to health, since proper neurotransmitter release is crucial to proper function of the nervous system, and defective transmitter release has been implicated in many psychiatric and neurological disorders.