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Patterning dendritic branches with environmental and neuronal surface molecules

用环境和神经元表面分子图案化树突分支

基本信息

批准号：
10311468
负责人：
KANG SHEN
金额：
$ 34万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-01 至 2024-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10311468
关键词：
Actins Address Affect Animals Area Axon Binding Binding Proteins Biochemical Biological Assay Biological Models Caenorhabditis elegans Cell model Cell physiology Cells Cis Tests Complex Control Animal Cytoplasmic Tail Cytoskeleton Dendrites Detection Development Drug Targeting Event F-Actin Family Feedback Funding Grant Growth Integral Membrane Protein Ion Channel Knowledge Ligand Binding Ligands Literature Locomotion Logic Lysosomes Mediating Modeling Modification Molecular Morphogenesis Motor Movement Muscle Muscle Cells Muscle Contraction Mutation Mutation Analysis Nerve Regeneration Neural Cell Adhesion Molecule L1 Neurodegenerative Disorders Neuromuscular Junction Neurons Neuropeptides Pathway interactions Pattern Peptide Hydrolases Process Proprioceptor Proprotein Convertases Proteins Receptor Signaling Regulation Research Sensory Signal Transduction Site Skin Surface System Testing Tight Junctions Work experimental study extracellular genetic analysis in vivo insight mutant nerve supply nervous system disorder neural circuit neuromuscular activity novel polymerization post stroke receptor recruit

项目摘要

In this grant, we propose to understand the molecular mechanisms of dendrite morphogenesis and function. Dendrite morphogenesis determines the connectivity of neurons. We are using a model cell (PVD in C elegans) to study this question. PVD is a proprioceptive neuron that senses muscle contraction and regulates animal movement. In our previous work, we identified the extracellular ligands and their receptor on PVD that guide the dendrite growth and branching. Here, we propose to understand how the receptor-ligand interaction triggers signaling mechanisms and leads to cytoskeletal modifications which eventually drives the morphogenesis events. We will also study how the neurons regulate receptor signaling using a drug target protein called KPC-1 to control guidance decisions. We will also understand how the PVD neurons sense muscle contraction using a putative mechanosensitive channel and how it regulates neuromuscular activity through a surprising neural circuit feedback mechanism. Through these experiments, we will gain insights in the molecular logic of dendrite development. We will identify novel mechanosensitive channels that are important for body movement regulation.

在这项资助中，我们提出要了解树突的分子机制形态发生和功能。枝晶形态决定了神经元我们正在使用一个模型细胞（线虫PVD）来研究这个问题。PVD是一种感觉肌肉收缩并调节动物运动的本体感受神经元。在我们以前的工作中，我们鉴定了PVD的胞外配体及其受体，引导枝晶生长和分支。在这里，我们建议了解受体-配体相互作用触发信号传导机制，最终驱动形态发生事件的修饰。我们还将研究如何神经元通过一种名为KPC-1的药物靶蛋白调节受体信号，控制指导决策。我们还将了解PVD神经元如何感知使用假定的机械敏感通道的肌肉收缩及其如何调节神经肌肉活动通过一个令人惊讶的神经回路反馈机制。通过这些实验，我们将对枝晶的分子逻辑有更深入的了解发展我们将确定新的机械敏感通道，这是重要的，身体运动调节