Role of ADF/cofilin in Neurotransmission

ADF/cofilin 在神经传递中的作用

• 批准号: 7118152
• 负责人: JANEL D FUNK
• 金额: $ 2.78万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-24 至 2007-09-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7118152
• 关键词: Drosophilidae; actin binding protein; actins; action potentials; biological signal transduction; cell communication molecule; cytoskeleton; electrostimulus; gene mutation; microfilaments; neural degeneration; neural transmission; phosphorylation; polymerization; predoctoral investigator; protein structure function; synaptic vesicles

DESCRIPTION (provided by applicant): Neurotransmission is a form of cellular communication that is truly astounding in its speed, efficiency of coupling electrical depolarization to molecular events, and ability to respond to changes in frequency of electrical stimulation without compromising the rhythm of neurotransmitter release. The secret to this adaptive feature of neurons may be in the selective use of synaptic vesicle populations: those that are poised for immediate release upon arrival of an action potential, and a "reserve pool" that is further removed from the presynaptic membrane, not to be used unless trains of stimuli demand their participation. The purpose of this project is to examine the role of actin dynamics in controlling use of this reserve pool. We will begin by assessing the effects of selectively stabilizing or destabilizing actin filaments on mobilization of these vesicles, and then characterize the regulation of dynamic actin reorganization in the nerve terminal by making activity-altering mutations in actin depolymerizing factor (ADF) as well as regulators of ADF activity. Solving the molecular ties between actin dynamics and the synaptic vesicle cycle will be prerequisite to our understanding of neurodegenerative diseases involving defective neurotransmission.

描述（由申请人提供）：神经传递是一种细胞通信的一种形式，其速度确实令人震惊，将电去极化耦合到分子事件的效率以及能够响应电刺激频率的变化而不会损害神经递质释放的节奏。 这种神经元这种适应性特征的秘诀可能在于选择性使用突触囊泡群体：在动作电位抵达时有望立即释放的神经元素，而“储备池”和突触前膜进一步去除的“储备池”，除非刺激需要刺激的列车，否则不得使用。 该项目的目的是检查肌动蛋白动力学在控制该储备池的使用中的作用。 我们将首先评估稳定或破坏肌动蛋白丝对动员这些囊泡的影响，然后通过使肌动蛋白去聚合因子（ADF）中的改变活性突变以及ADF活性调节剂来调节神经终末中动态肌动蛋白重组。 解决肌动蛋白动力学与突触囊泡周期之间的分子关系将是我们理解涉及缺陷神经传递的神经退行性疾病的先决条件。