REGULATION OF THE SYNAPTIC VESICLE CYCLE

突触小泡周期的调节

• 批准号: 6238042
• 负责人: REGIS B KELLY
• 金额: $ 21.51万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-05 至 1998-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6238042
• 关键词: FK506; HeLa cells; PC12 cells; cell differentiation; cyclic AMP; cyclosporines; dopamine; granule; membrane activity; neuropharmacology; neurotoxins; neurotransmitter transport; neurotrophic factors; phorbols; phosphatidate; protein isoforms; synaptic vesicles; transfection

The synapse is altered by learning and by prolonged exposure to psychoactive drugs.Release of neurotransmitter at the synapse depends on the rates at which synaptic vesicles fuse with the plasma membrane, then recycle and refill. Recently, proteins involved in the fusion step have been identified and shown to form a fusion complex of vesicle and plasma membrane proteins. In addition, an assay has been developed in this lab that screens for the proteins involved in vesicle recycling. The other two proposals also address vesicle refilling. There is evidence that one or more of these three steps in the synaptic cycle are modified by psychoactive drugs. in this proposal assays of fusion complexes and of synaptic vesicle biogenesis will be developed using the neuroendocrine, dopamine-secreting cell line, PC12, since dopamine pathways appear to be central to drug abuse. To determine how the molecules involved in these two steps of the synaptic vesicle cycle are regulated by short-term and long-term modifications, the assays will be used to detect changes in response to secretagogues, NGF, synaptic modulators and selected psychoactive substances.

突触通过学习和长时间接触而改变 精神活性药物。突触中神经递质的释放取决于 突触囊泡与质膜融合的速率，然后 回收和补充。最近，涉及融合步骤的蛋白质具有 被鉴定并显示形成囊泡和等离子体的融合复合物 膜蛋白。此外，该实验室已经开发了一种测定 筛选参与囊泡回收的蛋白质。另外两个 建议还解决了囊泡的补充。有证据表明一个或 突触周期中的这三个步骤中有更多的步骤通过 精神活性药物。在此提案分析中，融合络合物和 突触囊泡生物发生将使用神经内分泌， 多巴胺分泌细胞系PC12，因为多巴胺途径似乎是 吸毒的核心。确定分子如何参与这些 突触囊泡周期的两个步骤由短期调节， 长期修改，该测定将用于检测变化 对促分子，NGF，突触调节器和选定的响应 精神活性物质。