Brain Myosin5 and Synaptic Plasticity

脑肌球蛋白 5 和突触可塑性

• 批准号: 0517303
• 负责人: George Langford
• 金额: $ 4万
• 依托单位: Dartmouth College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0517303&HistoricalAwards=false
• 关键词: Brain; Myosin5; Synaptic; Plasticity

Brain Myosin5 and synaptic plasticityAbstract of projectThe human brain is a flexible structure that changes in response to experiences but it isnot fully understood how experience changes the brain at the cellular level and resultsin learning and memory. The question posed in this proposal is "what is the role ofthe actin-dependent molecular motor, brain myosin5, in experience-driven synapticplasticity, i.e how does myosin5 participate in synaptic strengthening?" Brainmyosin5 (Myosin-Va) has multiple functions that link it to synaptic plasticity. Ittransports vesicles as well as other kinds of cargo at axon terminals and dendriticspines. In addition, it is a constitutive component of the postsynaptic density.Previous studies have shown that myosin5 binds to kinesin (heteromotor complex)and functions as a molecular motor for the transport of endoplasmic reticulum (ER)vesicles. Those studies led to the following specific question to be addressed in thisproject: How is transport of ER vesicles by myosin5 and kinesin coordinated. Thespecific aims are as follows: The PI and his research group will isolate brain-specificbinding partners of myosin5 using affinity-based biochemical methods and identifythe proteins using proteomic approaches (brain-specific myosin5 proteome). Theresults from this proteomics screen will be used to determine which proteinsconstitute the myosin5/kinesin heteromotor complex. From the list of proteinsidentified by proteomics, they will identify signaling proteins that associate with themyosin5/kinesin motor complex and determine which of these signaling proteinsfunction to coordinate kinesin and myosin5 activity during transport of ER vesiclesusing an in vitro motility assay.Broader impacts resulting from the proposed activities: The broader impacts willinclude mentoring by the PI of minority students through the Ernest Everett JustProgram at Dartmouth, sponsoring undergraduate students engaged in independentresearch projects and honor's theses research in his laboratory and working withstudents from Spelman College and Morehouse College (2 HBCUs) who come toDartmouth as exchange students. In addition, the PI will continue to sponsorundergraduate students in his laboratory at the Marine Biological Laboratory, WoodsHole MA. Each summer he gives lectures on his research and provides mentoring tominority graduate students enrolled in the SPINES (Neuro) course at the MBL.

脑肌球蛋白与突触可塑性项目摘要人脑是一个灵活的结构，它会随着经验的变化而变化，但经验是如何在细胞水平上改变大脑并导致学习和记忆的，目前还不完全清楚。这个提议提出的问题是“肌动蛋白依赖的分子运动，脑肌球蛋白5在经验驱动的突触可塑性中的作用是什么，即肌球蛋白5是如何参与突触强化的？”脑肌球蛋白5 （Myosin-Va）具有多种与突触可塑性有关的功能。它在轴突末端和树突棘运输囊泡以及其他种类的货物。此外，它是突触后密度的组成部分。先前的研究表明，肌球蛋白5与运动蛋白（异动复合物）结合，并作为内质网（ER）囊泡运输的分子马达。这些研究导致以下具体问题需要在本项目中解决：肌球蛋白5和运动蛋白是如何协调内质网囊泡的运输的。具体目标如下：PI和他的研究小组将使用基于亲和力的生化方法分离脑特异性myosin5结合伙伴，并使用蛋白质组学方法（脑特异性myosin5蛋白质组学）鉴定蛋白质。蛋白质组学筛选的结果将用于确定哪些蛋白质构成肌球蛋白5/激酶异动复合物。从蛋白质组学鉴定的蛋白质列表中，他们将鉴定与肌球蛋白5/肌球蛋白运动复合物相关的信号蛋白，并通过体外运动测定确定哪些信号蛋白在内质网囊的运输过程中协调肌球蛋白和肌球蛋白5的活性。拟议活动产生的更广泛的影响：更广泛的影响将包括由达特茅斯大学欧内斯特·埃弗雷特正义计划的少数民族学生的PI指导，赞助从事独立研究项目的本科生，并在他的实验室进行荣誉论文研究，并与来自斯佩尔曼学院和莫豪斯学院（2个HBCUs）的学生一起作为交换生来到达特茅斯。此外，PI将继续资助他在WoodsHole MA海洋生物实验室的实验室的本科生。每年夏天，他都会就自己的研究发表演讲，并为参加MBL脊柱（神经）课程的少数族裔研究生提供指导。