Role of synaptotagmin IV in fast synaptic transmission

突触结合蛋白 IV 在快速突触传递中的作用

• 批准号: 6936173
• 负责人: JONATHAN T TING
• 金额: $ 3.18万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6936173
• 关键词: calcium binding protein; calcium flux; cell cell interaction; evoked potentials; exocytosis; genetically modified animals; hippocampus; laboratory mouse; neural plasticity; neural transmission; neuromuscular stimulator; neurons; neurotransmitter transport; polymerase chain reaction; predoctoral investigator; protein structure function; synapses; synaptic vesicles; synaptotagmin; tissue /cell culture

DESCRIPTION (provided by applicant): The goal of this project is to determine the role of Synaptotagmin (Syt) IV in the control of mammalian synaptic transmission. The 15 identified Syts comprise a family of calcium (Ca) binding proteins that generally regulate membrane trafficking events. Syts I, II, and IV are found in synaptic vesicle membranes, which suggests that these isoforms are important for neurotransmission. Recent evidence reveals that Syts I and II are primary Ca sensors for neurotransmission, but there is little consensus on the role of Syt IV. The Syt IV protein is strongly elevated following seizures and has diminished Ca binding relative to Syt I and other isoforms. This proposal focuses on two Specific Aims to determine the function of Syt IV. Specific Aim 1 tests the hypothesis that Syt IV is a Ca sensor that is less effective than Syt I in promoting neurotransmitter release. Specific Aim 2 tests the hypothesis that elevation of Syt IV (as occurs following seizure) reduces neurotransmission. The experimental design will employ viral-mediated Syt IV expression and electrophysiological measurement of neurotransmission in cultured mammalian neurons. Evidence in support of these hypotheses would suggest a neuroprotective role for Syt IV following seizures.

描述（由申请人提供）：该项目的目的是确定突触联蛋白（SYT）IV在控制哺乳动物突触传播中的作用。这15个确定的SYT包括一个通常调节膜运输事件的钙（CA）结合蛋白家族。 Syts I，II和IV在突触囊泡膜中发现，这表明这些同工型对于神经传递很重要。最近的证据表明，SYTS I和II是神经传递的主要CA传感器，但是SYT IV的作用几乎没有共识。癫痫发作后，SYT IV蛋白强烈升高，并且相对于SYT I和其他同工型的Ca结合减少了。该建议重点是确定SYT IV功能的两个特定目的。特定的目标1检验了Syt IV是CA传感器的假设，在促进神经递质释放方面的有效性不如SYT I有效。具体目标2检验了以下假设：SYT IV升高（如癫痫发作后发生）减少了神经传递。实验设计将采用病毒介导的SYT IV表达和对培养的哺乳动物神经元中神经传递的电生理测量。支持这些假设的证据表明，癫痫发作后SYT IV起神经保护作用。