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

• 批准号: 9767867
• 负责人: Tim Stearns
• 金额: $ 34万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 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/9767867
• 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; Cleaved cell; 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

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，我们建议了解树突的分子机制