THE ROLE OF AGRIN IN THE DEVELOPMENT OF CENTRAL NEURONS

AGRIN 在中枢神经元发育中的作用

基本信息

批准号：
7214180
负责人：
ADRIANA B. FERREIRA
金额：
$ 23.41万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-05-15 至 2009-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7214180
关键词：
Agrin Antisense Oligonucleotides Attention Belief Binding Biological Assay Biological Models Chromosome Pairing Coculture Techniques Computer information processing Defect Development Diagnosis Electron Microscopy Elements Extracellular Matrix Proteins Generations Hippocampus (Brain)Immunoprecipitation In Situ Knowledge Mediating Mediator of activation protein Motor Neurons Neuraxis Neurites Neurodegenerative Disorders Neuromuscular Junction Neurons Numbers Orphan Pattern Phenotype Play Positioning Attribute Prevention Process Proteins Rate Receptor Protein-Tyrosine Kinases Research Personnel Reverse Transcriptase Polymerase Chain Reaction Role Ror receptor tyrosine kinase Signal Pathway Spatial Distribution Staging Synapses Techniques Testing Western Blotting Work agrin receptor design homologous recombination immunocytochemistry null mutation programs receptor research study synaptogenesis

项目摘要

DESCRIPTION (provided by applicant): In the past two decades, a great deal of attention has been directed to the study of synaptogenesis in the mammalian central nervous system. Many of these studies are driven by the belief that the diagnosis and the prevention of synapse loss associated with several neurodegenerative diseases can be achieved through a better understanding of the basic mechanisms of synapse formation in central neurons. Although these mechanisms are not completely understood, it is tempting to speculate that proteins, such as agrin, that play a key role in the formation of the neuromuscular junction might also play an important role in the formation of synaptic contacts between neurons. Recently, we have shown that agrin differentially regulates the rates of axonal and dendritic elongation as well as synapse formation in hippocampal neurons. However, the agrin receptor(s) has yet to be identified in these neurons. The experiments proposed here are intended to test the following hypothesis: ror proteins, two tyrosine kinase receptors considered "orphan receptors", could mediate the effects of agrin on early stages of development in central neurons. A combination of techniques including: Western blot analysis, immunocytochemistry, RT-PCR, the generation of null mutations, binding assays, and immunoprecipitation will be used to analyze: 1) the pattern of expression and localization of ror 1 and ror 2 in central neurons; 2) the role of these tyrosine kinase receptors in neurite elongation and synapse formation; and 3) the participation of ror 1 and ror 2 in the agrin-signaling pathway.

描述（由申请人提供）：在过去的二十年中，已经大大关注了哺乳动物中枢神经系统突触发生的研究。这些研究中的许多研究是由相信与几种神经退行性疾病相关的诊断和预防突触损失可以通过更好地理解中枢神经元突触形成的基本机制来实现的。尽管这些机制尚未完全理解，但很容易推测蛋白质（例如Agrin）在神经肌肉结的形成中起关键作用，也可能在神经元之间突触接触的形成中起重要作用。最近，我们已经表明，Agrin差异调节海马神经元中轴突和树突伸长的速率以及突触形成。但是，在这些神经元中尚未鉴定Agrin受体。此处提出的实验旨在检验以下假设：ROR蛋白，两个被认为是“孤儿受体”的酪氨酸激酶受体可以介导Agrin对中央神经元发育早期阶段的影响。技术的结合包括：蛋白质印迹分析，免疫细胞化学，RT-PCR，无效突变，结合测定和免疫沉淀的产生将用于分析：1）中央神经元中ROR 1和ROR 2的表达和定位模式； 2）这些酪氨酸激酶受体在神经突伸长和突触形成中的作用； 3）ROR 1和ROR 2的参与在Agrin信号途径中。