RUI: Modulation of synaptic vesicle exocytosis in C. elegans

RUI：秀丽隐杆线虫突触小泡胞吐作用的调节

• 批准号: 0956598
• 负责人: Andrea Holgado
• 金额: $ 69.88万
• 依托单位: Southwestern Oklahoma State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-15 至 2016-03-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0956598&HistoricalAwards=false
• 关键词: RUI; Modulation; synaptic; vesicle; exocytosis

Cells release various products to the outside through a process called exocytosis. In the nervous system, exocytosis mediates the release of chemicals including neurotransmitters, and a number of highly conserved proteins have been shown to control this process. In this project, a hypothesis will be tested that one protein originally discovered in yeast, VSM-1, may regulate exocytosis in the nervous system of multicellular animals. To test this hypothesis, the impact of mutating the gene coding for VSM-1 will be examined by studying the resulting changes at the level of molecules, cells, and whole organisms in C. elegans. At the cellular level, it will be determined if communication between neurons is impaired in mutants lacking the gene. Finally, whole mutant animals will be examined using pharmacological tests and fluorescent microscopy. Preliminary unpublished data showed that C. elegans strains containing the mutation in the VSM-1 gene are hyperactive and have more nerve endings than wild type animals. Insights into the mechanism of VSM-1 from this proposal will advance understanding of the nervous system of higher animals, including humans, because there are no reports yet on the function of VSM-1 in multicellular animals. The proposed research will also significantly enhance and promote students' training in the field of neuroscience since it will primarily be conducted by undergraduate students enrolled at Southwestern Oklahoma State University (SWOSU), a teaching institution in rural western Oklahoma with a growing commitment to research.

细胞通过一种叫做胞吐作用的过程向外界释放各种产物。在神经系统中，胞吐作用调节包括神经递质在内的化学物质的释放，许多高度保守的蛋白质已被证明控制着这一过程。在这个项目中，将检验一种假说，即最初在酵母中发现的一种蛋白质VSM-1可能调节多细胞动物神经系统的胞吐。为了验证这一假设，将通过研究在线虫中分子、细胞和整个生物体水平上由此产生的变化来检验突变VSM-1基因的影响。在细胞水平上，将确定缺乏该基因的突变体是否会损害神经元之间的通信。最后，将使用药理学测试和荧光显微镜对整个突变动物进行检查。未发表的初步数据显示，含有VSM-1基因突变的线虫菌株比野生动物更活跃，神经末梢更多。从这一建议中深入了解VSM-1的机制将促进对包括人类在内的高等动物神经系统的了解，因为目前还没有关于VSM-1在多细胞动物中的功能的报告。这项拟议的研究还将显著加强和促进学生在神经科学领域的培训，因为它将主要由西南俄克拉荷马州立大学(SWOSU)招收的本科生进行，SWOSU是一家位于俄克拉荷马州西部农村的教学机构，对研究的承诺越来越大。