REGULATION OF CHOLINERGIC FUNCTION IN CAENORHABDITIS ELEGANS

秀丽隐杆线虫胆碱能功能的调节

• 批准号: 7725102
• 负责人: DENNIS L FRISBY
• 金额: $ 10.84万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7725102
• 关键词: Acetylcholine; Anabolism; Caenorhabditis elegans; Choline O-Acetyltransferase; Cholinergic Agents; Complex; Computer Retrieval of Information on Scientific Projects Database; Congenital Myasthenic Syndromes; Defect; Disease; Funding; Gene Expression Regulation; Genes; Grant; Human; Individual; Institution; Knowledge; Mammals; Molecular; Nematoda; Nervous system structure; Operon; Promoter Regions; Protein Isoforms; Proteins; Regulation; Research; Research Personnel; Resources; Soil; Source; Structure; Synaptic Vesicles; United States National Institutes of Health; acetylcholine transporter; cholinergic; cholinergic neuron; design; novel; promoter; research study; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Despite intensive study, the cholinergic nervous system is poorly understood at the molecular level. Since defects in cholinergic function have been implicated in human disorders, such as Alzhiemer's disease and congenital myasthenic syndromes, a more complete knowledge of the molecular mechanisms that control the cholinergic nervous system might contribute to a better understanding of the mechanisms involved in these disorders. The experiments outlined in this proposal are designed to continue our analysis of the cholinergic locus (cha-1 - unc-17) in the soil nematode, Caenorhabditis elegans. The cha-1 gene encodes choline acetyltransferase (ChAT), required for acetylcholine biosynthesis, and the unc-17 gene encodes the vesicular acetylcholine transporter (VAChT), which is necessary for synaptic vesicle loading. These genes comprise a cholinergic "operon" with a novel structure that is conserved from nematodes to mammals, suggesting that the overall structure may be important for proper regulation. We have already analyzed the upstream promoter region of this locus, and have identified and characterized specific regulatory sequences required for expression in subsets of cholinergic neurons. In addition, we now have evidence for a cha-1-specific promoter in C. elegans, expression from which produces a previously unidentified isoform of ChAT (CHA-1B). We now wish to use the information and tools we have developed to analyze the regulation of these genes and the contribution of the different isoforms of the ChAT to cholinergic function. The specific aims of the research are: (1) To identify proteins required for regulation of the cha-1 - unc-17 complex. (2) Study the individual contributions of the CHA-1A (expressed from the upstream promoter) and CHA-1B isoforms to cholinergic function.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 尽管进行了深入的研究，但在分子水平上，胆碱能神经系统的了解很少。 由于胆碱能功能的缺陷已与人类疾病有关，例如阿尔茨海默氏病和联合肌肌局综合征，因此对控制胆碱能神经系统的分子机制的更完整了解可能有助于更好地了解这些疾病中所涉及的机制。 该提案中概述的实验旨在继续我们对秀丽隐杆线虫土壤线虫中胆碱能基因座（CHA-1-UNC-17）的分析。 CHA-1基因编码乙酰胆碱生物合成所需的胆碱乙酰转移酶（CHAT），而UNC-17基因编码囊泡乙酰胆碱转运蛋白（VACHT），这对于突触囊泡负荷是必需的。 这些基因包含一种胆碱能的“操纵子”，其新型结构从线虫到哺乳动物是保守的，这表明整体结构对于适当的调节可能很重要。 我们已经分析了该基因座的上游启动子区域，并确定并表征了胆碱能神经元亚群所需的特定调节序列。 此外，我们现在有证据表明秀丽隐杆线虫中的CHA-1特异性启动子，从而产生了以前未鉴定的CHAT同工型（CHA-1B）。 现在，我们希望使用我们开发的信息和工具来分析这些基因的调节以及聊天的不同同工型对胆碱能功能的贡献。 研究的具体目的是：（1）确定调节CHA-1-UNC-17复合物所需的蛋白质。 （2）研究CHA-1A（从上游启动子表达）和CHA-1B同工型对胆碱能功能的个体贡献。