MUTATIONAL ANALYSIS OF A NICOTINIC ACETYLCHOLINE RECEPTOR FROM DROSOPHILA

果蝇烟碱乙酰胆碱受体的突变分析

基本信息

批准号：
6450704
负责人：
THOMAS SCHMIDT-GLENEWINKEL
金额：
$ 5.95万
依托单位：
HUNTER COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-04-01 至 2002-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6450704
关键词：
Drosophilidae Escherichia coli X ray acetylcholine biological signal transduction developmental neurobiology gene mutation genetic screening in situ hybridization mathematical model neurotransmitter receptor nicotinic receptors point mutation

项目摘要

Acetylcholine receptors are key elements of synaptic transmission and neuronal signal transduction. The proposed studies will focus on the role of the neuronal nicotinic acetylcholine receptor during development of the nervous system of Drosophila. We will carry out a genetic analysis of this receptor in vivo by introducing mutations into two genes encoding an alpha-subunit (als) and beta-like subunit (ard). These two subunits form part of one of the subtypes of a neuronal nicotinic acetylcholine receptors in Drosophila. Results from these studies will allow us to analyze the effect of various mutations in the receptor on the development, structure and function of the nervous system. These studies have also biomedical relevance since it was found recently that mutations in the receptor in humans lead to epilepsy. In the second part of our proposal we will carry out a genetic screen to identify targets of nicotine action in the nervous system of Drosophila. The molecular mechanisms to be identified in nicotine action might be part of the signal transduction cascade through nicotinic acetylcholine receptors (nAChR); alternatively nicotine action might involve components yet to be identified. Knowledge of these pathways might contribute to our understanding of nicotine addiction in humans. Structural analysis of this neurotransmitter receptors has also significance for a rational design of insecticides.

乙酰胆碱受体是突触传递和神经元信号转导的关键元件。拟议的研究将重点关注神经元烟碱乙酰胆碱受体在果蝇神经系统发育过程中的作用。我们将通过在编码α亚基（als）和β样亚基（ard）的两个基因中引入突变来对该受体进行体内遗传分析。这两个亚基构成果蝇神经元烟碱乙酰胆碱受体亚型之一的一部分。这些研究的结果将使我们能够分析受体的各种突变对神经系统发育、结构和功能的影响。这些研究还具有生物医学意义，因为最近发现人类受体的突变会导致癫痫。在我们提案的第二部分，我们将进行基因筛选，以确定果蝇神经系统中尼古丁作用的目标。尼古丁作用的分子机制可能是通过烟碱乙酰胆碱受体（nAChR）的信号转导级联的一部分；另外，尼古丁的作用可能涉及尚未确定的成分。了解这些途径可能有助于我们了解人类尼古丁成瘾。这种神经递质受体的结构分析对于杀虫剂的合理设计也具有重要意义。