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Regulation of Axonal Transport At Branch Junctions

分支连接处轴突运输的调节

基本信息

批准号：
10383151
负责人：
Le Ma
金额：
$ 34.13万
依托单位：
THOMAS JEFFERSON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10383151
关键词：
Adult Afferent Neurons Axon Axonal Transport Behavior Biological Cells Color Cytoskeleton Data Dendrites Development Disease Distal Dynein ATPase Embryo Embryonic Development Epilepsy Functional Regeneration Functional disorder Genetic Goals Growth Health Human Impairment In Situ Injury Kinesin Knowledge Light Link Location Lysosomes MAP1 Microtubule-Associated Protein Mediating Membrane Membrane Proteins Microtubule-Associated Proteins Microtubules Mission Mitochondria Modeling Molecular Morphogenesis Motor Nervous System Physiology Nervous system structure Neurodegenerative Disorders Neurons Oranges Presynaptic Terminals Proteins RNA Recovery of Function Regulation Research Role Route Shapes Signal Transduction Slice Specificity Speed Spinal Ganglia Synapses Testing Time United States National Institutes of Health anterograde transport base cell age cell type experimental study insight interest molecular imaging nerve injury nervous system disorder novel optogenetics preference recruit response synaptic function tool trafficking

项目摘要

Axonal transport is essential to development and function of the nervous system. Axonal transport relies on motor proteins (kinesins and dynein) to move protein, membrane and RNA cargos along microtubules. It is especially important to long and often highly branched axons that requires building blocks made in the cell body or signals received at axonal terminals to be transported for long distance. Recently studies have identified many regulatory mechanisms, including the interactions between motor proteins with lattice-bound microtubule associated proteins (MAPs), in different axonal regions. However, how axonal transport is regulated to steer cargos into and out of branches is not well understood. This is an outstanding problem as axonal branches are present throughout the nervous system. They not only define neuronal shape, but also control synaptic connectivity and specificity, influence structural plasticity, and promote functional regeneration after injury. The proposed study will tackle this under-studied problem by building on our long-term interest in branch morphogenesis and cytoskeleton regulation as well as a recent discovery of a MAP in branch development and transport regulation. Our preliminary data showed that transport at branch junctions is highly selective as cargos are preferentially transported into growing branches. In addition, we also found that MAP7, a MAP that is localized to branch junctions and interacts with the plus end motor kinesin-1, influences transport behavior and branch growth. We thus hypothesize that axonal transport at branch junctions is controlled by a selective routing mechanism that is mediated by specific motor-MAP interactions. To test this hypothesis, we will: 1) establish a functional link between selective transport and branch growth; 2) dissect the mechanism mediated by MAP7; and 3) establish selective routing as a common feature in axonal transport. By focusing on an important region of the axon that has not been studied in the past, these studies will not only fill in a gap in our understanding of axonal transport, but also provide new insights into synaptic development and function. Given the importance of axonal transport in many neurological and neurodegenerative disorders, and the association of MAP7 and kinesin-1 with epilepsy and ALS, our proposed studies of a basic neuronal cell biological problem will provide new knowledge to uncover disease mechanisms, and thus are highly relevant to the NIH mission to understand and enhance human health.

轴突转运对神经系统的发育和功能至关重要。轴突运输