Molecular mechanisms underlying activity-induced synaptic remodeling

活动诱导的突触重塑的分子机制

基本信息

批准号：
10438584
负责人：
KAREN T CHANG
金额：
$ 43.65万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10438584
关键词：
Acute Address Affect Alzheimer&apos s Disease Brain Cell Adhesion Molecules Cognitive deficits Complex Cues Data Defect Development Disease Drosophila genus Genes Genetic Genetic Screening Glutamate Receptor Glutamates Goals Growth Growth and Development function Impairment Integrins Lead Learning Link Memory Mental disorders Modification Molecular Morphology Names National Institute of Neurological Disorders and Stroke Nervous system structure Neuromuscular Junction Neurons Pathway interactions Play Process Proteins Publishing Research Role Schizophrenia Signal Pathway Signal Transduction Stimulus Structure Synapses Synaptic plasticity Testing Therapeutic Work calmodulin-dependent protein kinase II experimental study extracellular functional plasticity human disease in vivo insight mutant nervous system disorder neuron development neuronal circuitry new therapeutic target novel novel therapeutic intervention prevent receptor response

项目摘要

The ability of neurons to rapidly modify synaptic structure and strength in response to neuronal activity, a process called activity-induced structural and functional plasticity, is crucial for neuronal development and complex brain functions such as learning and memory. Recent evidence suggests that integrin receptors, a major class of cell adhesion molecules, play an important role in synaptic plasticity. However, how neurons dynamically couple synaptic demand to structural remodeling, and what activates integrin during neuronal activity remain elusive. My lab has recently identified a novel protein named Shriveled (Shv) that activates integrin via outside-in signaling. We now have evidence showing that Shv is selectively released during intense neuronal activity, and that shv mutant cannot undergo synaptic remodeling in response to neuronal activity at the Drosophila neuromuscular junction. In this proposal, we will: (1) investigate the role that Shv plays during development to regulate synaptic growth and function; (2) delineate how neuronal activity regulates Shv release and activity-induced structural and functional plasticity; (3) elucidate molecular and cellular mechanisms underlying activity-induced structural remodeling. As a healthy nervous system depends on the ability of neurons to dynamically adjust synaptic strength and modify synaptic structure in response to neuronal activity, elucidating Shv functions and mechanisms underlying activity-induced synaptic remodeling may lead to new therapeutic strategies to treat or prevent neurological and psychiatric disorders.

神经元响应神经元的信号而快速改变突触结构和强度的能力活动，一个称为活动诱导的结构和功能可塑性的过程，对于神经元发育和复杂的大脑功能，例如学习和记忆。最近的有证据表明，整合素受体是一类主要的细胞粘附分子，在在突触可塑性中发挥重要作用。然而，神经元如何动态耦合突触对结构重塑的需求以及神经元活动期间激活整合素的因素仍然存在难以捉摸。我的实验室最近发现了一种名为 Shriveled (Shv) 的新型蛋白质，它可以激活通过由外向内信号传递的整合素。我们现在有证据表明Shv被选择性释放在强烈的神经元活动期间，shv 突变体不能进行突触重塑对果蝇神经肌肉接头神经元活动的反应。在这个提案中，我们将：（1）研究 Shv 在发育过程中发挥的调节突触生长和功能; (2) 描绘神经元活动如何调节Shv释放和活动诱导结构和功能的可塑性； (3) 阐明潜在的分子和细胞机制活动引起的结构重塑。健康的神经系统取决于神经元动态调整突触强度并修改突触结构以响应神经元活动，阐明 Shv 功能和活动诱导的机制突触重塑可能会带来新的治疗策略来治疗或预防神经系统和精神疾病。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Identification of secretory autophagy as a mechanism modulating activity-induced synaptic remodeling.

DOI：
10.1073/pnas.2315958121
发表时间：
2024-04
期刊：
Proceedings of the National Academy of Sciences of the United States of America
影响因子：
11.1
作者：
Yen-Ching Chang;Yuan Gao;Joo Yeun Lee;Yi-Jheng Peng;J. Langen;Karen T. Chang
通讯作者：
Yen-Ching Chang;Yuan Gao;Joo Yeun Lee;Yi-Jheng Peng;J. Langen;Karen T. Chang

Minibrain kinase and calcineurin coordinate activity-dependent bulk endocytosis through synaptojanin.