MOLECULAR BIOLOGY OF NEUROTRANSMITTER RECEPTORS

这项计划是为了表征基因和蛋白质的结构和 两个主要多基因神经递质受体的研究进展 家人。第一个基因家族包括肾上腺素能、毒鼠碱、视蛋白、 5-羟色胺和章鱼胺受体，第二种含有尼古丁 胆碱能、GABA/苯二氮卓类NMDA和甘氨酸受体。具体的 目的是克隆和测序这两种受体的基因。 多基因家族；获得高密度受体表达并使用 部分确定完整受体结构的表达蛋白 通过计算机增强的分子模拟；以确定 神经递质受体基因家族；寻找和鉴定 受体基因多态性。到目前为止，我们已经克隆并测序了一个 来自两个多基因家族的大量受体基因。这些 包括人和大鼠c DNA中几种α和β肾上腺素能受体 和基因组文库；来自人、大鼠和 果蝇基因组文库。果蝇的章鱼胺受体；人类 GABA/苯二氮卓类受体的α和β亚基；烟碱 蝗虫和线虫的受体。例如，人类GABAβ1 亚基已经被克隆和测序，并定位在4号染色体上。 基因全长超过65kb，由9个外显子组成。外显子和剪接位点 在人类的其他GABA受体亚基中高度保守 物种。表达独特神经递质的永久性细胞系 受体蛋白提供了关于 神经递质激活受体的机制。

This project is to characterize the gene and protein structure and evolution of neurotransmitter receptors belonging to two major multigene families. The first gene family comprises adrenergic, muscarinic, opsin, serotonin and octopamine receptors and the second comprises nicotinic cholinergic, GABA/benzodiazepine NMDA, and glycine receptors. The specific aims are to clone and sequence the genes for receptors in these two multigene families; to obtain high density receptor expression and to use the expressed proteins to determine the complete receptor structure in part by computer enhanced molecular modeling; to determine the evolution of the neurotransmitter receptor gene families; and to search for and characterize receptor gene polymorphisms. To date, we have cloned and sequenced a significant number of receptor genes from both multigene families. These include several alpha and beta-adrenergic receptors from human and rat cDNA and genomic libraries; muscarinic cholinergic receptor from human, rat and Drosophila genomic libraries. Octopamine receptors for Drosophila; human alpha and beta subunits of the GABA/benzodiazepine receptor; and nicotinic receptors from locusts and C. elegans. For example the human GABA beta 1 subunit has been cloned and sequenced and localized to chromosome 4. This gene is over 65kb and is composed of nine exons. The exons and splice sites are highly conserved in other GABA receptor subunits from humans and lower species. Permanent cell lines expressing the unique neurotransmitter receptor proteins are providing key new information concerning the mechanism of receptors activation by neurotransmitters.