MOLECULAR BIOLOGY OF NEUROTRANSMITTER RECEPTORS

该项目旨在描述基因和蛋白质结构， 属于两个主要多基因的神经递质受体的进化 家庭 这些基因家族包括肾上腺素能，毒蕈碱， 视蛋白、5-羟色胺和章鱼胺受体等;以及第二种 包括烟碱胆碱能、GABA/苯二氮卓类、NMDA和 甘氨酸受体 具体目标是：克隆和测序 这两个多基因家族中的受体基因;以获得 高密度受体表达，并使用表达的蛋白质 确定完整的受体结构，部分通过计算机增强 分子建模;以确定神经递质的进化 受体基因家族;寻找和表征受体基因 多态性 到目前为止，我们已经克隆和测序了大量的 来自两个多基因家族的受体基因。 其中包括几个 来自人和大鼠cDNA和基因组的α和β-肾上腺素能受体 文库;来自人、大鼠和大鼠的毒蕈碱胆碱能受体， 来自果蝇的章鱼胺受体;和 蝗虫烟碱受体和C.优雅 最近，我们 克隆并测序了人类GABA-A受体β-1和β-3 亚基，大鼠m3毒蕈碱受体基因组克隆，大鼠脂肪 细胞特异性（β-3）肾上腺素能受体，几个C.烟碱美香 受体亚单位，和一个尚未鉴定的7-跨膜受体 来自果蝇。 此外，十几个受体克隆具有 在我们的人脑cDNA项目[ZO 1 NS 02806 -02]中分离到，包括 N-甲酰肽受体、大麻素受体和 α-2B肾上腺素能受体 一个主要的发现是 人类GABA β-3亚基基因位于普拉德-威利基因座 15号染色体上的Angleman综合征和Angleman综合征。

This project is to characterize the gene and protein structure and evolution of neurotransmitter receptors belonging to two major multigene families. The gene families are those comprising adrenergic, muscarinic, opsin, serotonin and octopamine receptors, among others; and the second family comprising 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 receptors from human, rat, and Drosophila genomic libraries; octopamine receptors from Drosophila; and nicotinic receptors from locusts and C. elegans. Most recently, we have cloned and sequenced the human GABA-A receptor beta- 1 and beta-3 subunits, a rat m3 muscarinic receptor genomic clone, the rat fat cell-specific (beta-3) adrenergic receptor, several C. elegans nicotinic receptor subunits, and an as yet unidentified 7-transmembrane receptor from Drosophila. In addition, more than a dozen receptor clones have been isolated in our human brain cDNA project [ZO1 NS02806-02], including the N-formylpeptide receptor, the cannabinoid receptor, and the alpha-2B-adrenergic receptor. A major finding has been the discovery that the human GABA beta-3 subunit gene lies in the locus of Prader-Willi syndrome and Angleman Syndrome on chromosome 15.