MOLECULAR BIOLOGY OF NEUROTRANSMITTER RECEPTORS

神经递质受体的分子生物学

• 批准号: 3945307
• 负责人: J C VENTER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3945307
• 关键词: aminoacid; beta adrenergic agent; brain cell; developmental genetics; evolution; gene expression; gene mutation; genetic transduction; human tissue; ligands; molecular biology; molecular cloning; molecular genetics; mutagens; mutant; neurophysiology; nucleic acid sequence; species difference; tissue /cell culture; aminoacid; beta adrenergic agent; brain cell; developmental genetics; evolution; gene expression; gene mutation; genetic transduction; human tissue; ligands; molecular biology; molecular cloning; molecular genetics; mutagens; mutant; neurophysiology; nucleic acid sequence; species difference; tissue /cell culture

Recently, we published a paper on Cloning and Sequence Analysis of the Human Brain beta-Adrenergic Receptor (FEBS Lett. 211:200-206, 1987). In a recent review concerning the evolution of adrenergic and cholinergic receptors we further postulated that the muscarinic cholinergic receptor has existed for over 600 million years (Prog. Neurobiol., in press) Pharmacological and biochemical evidence suggests that the beta-adrenergic receptor appeared later in evolution raising the possibility that it evolved as a result of gene duplication. In order to further answer questions concerning receptor evoltion we are in the process of cloning beta-adrenergic and muscarinic cholinergic receptors from shark and Drosophila tissue. The cloning of neural receptor genes also allowed us to study the structure-function relationship of these receptors by site-directed mutagenesis. We have successfully expressed the human beta2-adrenergic receptor gene is a mouse cell line previously lacking the functional receptor. A series of single amino acid substitution mutants have also been made and are in the process of being characterized. Study of these mutants should help us to locate those important residues responsible for ligand binding, signal transduction or maintenance of structural integrity. *(Transferred from LNP on 7/87).

最近，我们发表了有关克隆和序列分析的论文 人脑β-肾上腺素能受体（Febs Lett。 211：200-206，1987）。 在最近有关进化的评论中 肾上腺素能和胆碱能受体我们进一步假设 毒蕈碱胆碱能受体已有600多个 百万年（媒体中的神经bor。）药理和 生化证据表明β-肾上腺素能受体 后来出现的进化提高了它进化的可能性 由于基因复制。 为了进一步回答 有关受体evoltion的问题我们正在 克隆β-肾上腺素和毒蕈碱胆碱能受体 来自鲨鱼和果蝇组织。 神经受体的克隆 基因还使我们能够研究结构功能关系 这些受体通过位置定向的诱变。 我们有 成功表达了人beta2-肾上腺素受体基因 是先前缺乏功能受体的小鼠细胞系。 一个 一系列单氨基酸取代突变体也已经 制造并正在表征。 研究 这些突变体应帮助我们找到那些重要的残留物 负责配体结合，信号转导或维护 结构完整性。 *（从7/87转移从LNP转移）。