Genetic Regulation of Acetylcholine Synthesis

本研究项目的目的是继续对土壤线虫的char-1基因复合体进行分子、遗传和生化分析。CHAR-1是胆碱乙酰转移酶的结构基因，胆碱乙酰转移酶合成神经递质乙酰胆碱。以往的证据表明，线虫胆碱乙酰转移酶蛋白可能由多个结构和功能结构域组成，人们对确定基因的组织和蛋白质的结构很感兴趣。此外，还将研究神经发育过程中胆碱乙酰转移酶的空间和时间控制。线虫之所以被用于这些研究，是因为它的神经系统简单，易于进行遗传分析，并且可以使用“转座子标记”技术从这种生物中克隆基因。这种最近的方法已经被用来“标记”和克隆部分CHA-1复合体。针对胆碱乙酰转移酶分子特定区域的抗体将被分离出来。分离的区域将用于胆碱乙酰转移酶结构的生化研究和分析乙酰胆碱利用神经元的发育的解剖学研究。获得的有关正常基因和酶的信息将用于分析神经结构和神经递质功能缺陷的突变体。

The goal of this research project is to continue molecular, genetic and biochemical analyses of the char-1 gene complex from the soil nematode Caenorhabditis elegans. Char-1 is the structural gene for choline acetyltransferase, the enzyme which synthesizes the neurotransmitter acetylcholine. Previously obtained evidence suggests that the choline acetyltransferase protein in C. elegans may consists of multiple structural and functional domains, and there is interest in determining the organization of the gene and the structure of the protein. In addition, investigations on the spatial and temporal control of choline acetyltransferase will be performed during neural development. C. elegans is being used for these studies because of its simple nervous system, its ease of genetic analysis, and the availability of the technique of "transposon tagging" to clone genes from this organism. This recent approach has been utilized to "tag" and clone part of the cha-1 complex. Antibodies directed against specific regions of the choline acetyltransferase molecule will be isolated. The isolated regions will be used in biochemical studies of choline acetyltransferase structure and in anatomical studies to analyze the development of acetylcholine-utilizing neurons. The information obtained about the normal gene and enzyme will be used to analyze mutants defective in neural structure and neurotransmitter function.