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Molecular determinants and function of axonal actin assemblies

轴突肌动蛋白组件的分子决定因素和功能

基本信息

批准号：
9981838
负责人：
Subhojit Roy
金额：
$ 34.67万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-01-15 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9981838
关键词：
Actin-Binding Protein Actins Address Algorithms Architecture Attenuated Axon Axonal Transport Biological Assay Biological Models Biology Caenorhabditis elegans Cell membrane Cells Cellular biology Clustered Regularly Interspaced Short Palindromic Repeats Cytoskeletal Modeling Cytoskeleton DNA Data Defect Distal EMS1 gene Endosomes Eukaryota Event Filament Generations Goals Growth Cones Homeostasis Image Investments Knowledge Learning Light Maintenance Metabolic Microfilaments Microfluidics Microscopic Microscopy Microtubules Molecular Mutation Names Neurobiology Neurodegenerative Disorders Neurodevelopmental Disorder Neurons Pattern Periodicity Pharmacology Study Physiological Polymers Protein Family Proteins Reporting Research Personnel Resolution Role Signal Transduction Stains Structure Surface Synapses Techniques Testing Vesicle Visualization autism spectrum disorder base beta Actin cofilin depolymerization experimental study fascinate human disease in vivo in vivo Model insight knock-down light microscopy migration monomer novel presynaptic small hairpin RNA synaptic function

项目摘要

The overall goal of this application is to clarify the molecular organization and function of enigmatic axonal actin assemblies that my lab recently discovered. Actin organization along axon shafts has been relatively ignored for decades, probably because routine staining – using the classic actin-filament marker phalloidin – only shows a patchy, uninteresting pattern. However, recent studies from us and others' using super-resolution microscopy and low-light imaging have revealed a hidden world of actin in axon shafts – replete with elaborate circumferential rings underneath the plasma membrane, and rapidly elongating linear filaments along the axis of the axon shaft. We have been fortunate to be at the forefront of these discoveries, and our studies have revealed fascinating actin dynamics in axons. Specifically, we found that axons have focal “hotspots” of actin – spaced ~ 3-4 µm apart – where actin continuously polymerizes and depolymerizes. These hotspots give rise to long actin filaments that rapidly (and bidirectionally) elongate along the axon shaft (we named these “actin trails”). Actin rings, trails and hotspots are seen in axons in vivo, and we will use in vivo model systems in this proposal as well. Although the overall assemblies have been seen, molecular events underlying the generation and maintenance of these structures is unclear. Importantly, their functional roles in axons are unknown. Here we propose three specific aims to clarify the organization and function of these newly-discovered actin assemblies: Aim #1: Identify mechanisms initiating actin trails in axons. Aim #2: Identify mechanisms elongating actin trails in axons. Aim #3: Determine functions of axonal actin assemblies.

本应用程序的总体目标是阐明神秘的轴突肌动蛋白的分子组织和功能