INTERACTION OF RAB3A W/ SYNAPTIC VESICLES

RAB3A 与突触小泡的相互作用

• 批准号: 6219612
• 负责人: John A. Glomset
• 金额: $ 5.72万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6219612
• 关键词: human tissue; nervous system; proteins

We showed previously that Ca2+ and the Ca2+-binding protein, calmodulin, can act together to displace the low molecular mass GTPase, Rab 3A from macaque brain prefrontal cortex synaptic vesicle membranes. This finding was of potential interest because synaptic vesicle-bound Rab 3A is thought to influence the Ca2+-triggered release of neurotransmitters from axonal termini. The fact that Ca2+/calmodulin can displace Rab 3A from synaptic vesicle membranes in vitro raises the possibility that Ca2+/calmodulin may have a similar effect in vivo. During the past year we explored this possibility in a collaborative study with investigators at the University of Lausanne in Switzerland. The results of the study showed that a mutant form of Rab 3 that cannot bind Ca2+/calmodulin has no effect on stimulated exocytotic events. This suggests that the complex of Rab 3 with Ca2+/calmodulin that is normally generated in response to elevated concentrations of Ca2+ may reduce the numbe r of exocy totic events that occur in response to secretory stimuli. FUNDING NIH grant RR00166 and the Howard Hughes Medical Institute.

我们以前表明，钙离子和钙离子结合蛋白， 钙调素，可以共同作用，以取代低分子量 猕猴脑前额叶皮层突触囊泡中GTdR，Rab 3A 膜。 这一发现具有潜在的意义，因为突触 囊泡结合的Rab 3A被认为影响Ca 2+触发的 轴突末梢释放神经递质。 的事实 Ca ~（2+）/钙调素可以从突触囊泡膜上置换Rab 3A， 体外提高了Ca 2 +/钙调素可能具有类似的 体内效应 在过去的一年里，我们探讨了这种可能性， 一项与洛桑大学研究人员的合作研究 在瑞士 研究结果表明， Rab 3不能结合Ca ~（2+）/钙调素，对刺激的 胞吐事件。 这表明Rab 3与 Ca 2 +/钙调蛋白，通常是响应于升高的 Ca ~（2+）浓度可减少胞吐事件的数量 是对分泌刺激的反应 资助NIH赠款 RR 00166和霍华德休斯医学研究所。