Molecular and Genetic Analysis of Presynaptic Proteins

突触前蛋白的分子和遗传分析

• 批准号: 6892154
• 负责人: James B. Rand
• 金额: $ 33.11万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6892154
• 关键词: Caenorhabditis elegans; complementary DNA; electrophysiology; gene expression; immunocytochemistry; molecular genetics; nerve /myelin protein; neurotransmitter transport; protein protein interaction; suppressor mutations; synaptic vesicles; synaptogenesis; tissue /cell culture; yeast two hybrid system

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.

描述（由申请人提供）：我们的目标是继续我们对秀丽隐杆线虫线虫线虫中突触传播的分子和遗传分析。秀丽隐杆线虫因其简单的神经系统，遗传和分子分析的易度性以及其基因组的完整测序而被用于这些研究。拟议的研究基于最新结果和最新技术进步。这三个广泛的目标是：（1）深入分析最近描述的RIP-1基因，该基因编码了一种非常大的蛋白质，该蛋白质被认为为突触前神经末端的成分提供了“分子支架”； （2）开始研究神经末端中使用的机制，以调节包装到每个突触囊泡中的神经递质量； （3）使用秀丽隐杆线虫细胞培养系统继续进行研究，以分析体外突触发育和功能。拟议的研究将扩展我们先前对秀丽隐杆线虫的突触结构和神经递质功能的分析，并包括在调节囊泡含量的调节中分离突变体的分离，以及鉴定特定分子和信号通路所需的特定分子和信号通路，以适当调节定量大小。尽管这是基础研究，但显然与健康有关，因为适当的神经递质释放对于神经系统的适当功能至关重要，并且有缺陷的发射机释放与许多精神病和神经系统疾病有关。