PROPERTIES OF AXONAL TUBULIN RELATED TO NEURONAL GROWTH

轴突微管蛋白与神经元生长相关的特性

• 批准号: 6139475
• 负责人: SCOTT THOMAS BRADY
• 金额: $ 21.9万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-04-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6139475
• 关键词: Schwann cells; axon; axoplasm; cell cell interaction; cell differentiation; cytoskeleton; electron microscopy; laboratory mouse; microtubules; myelin; myelination; nervous system regeneration; neurofilament proteins; neurogenesis; oligodendroglia; paclitaxel; phosphatase inhibitor; phosphorylation; posttranslational modifications; protein tyrosine kinase; sciatic nerve; second messengers; tissue /cell culture; transfection /expression vector; tubulin

DESCRIPTION (Adapted from Applicant's Abstract): The neuronal cytoskeleton is a dynamic, highly specialized set of structures that plays critical roles in many aspects of the nervous system, ranging from generation and maintenance of neuronal morphologies to defining functional domains of a neuron. To serve these functions, the components of the cytoskeleton must be biochemically specialized to control organization and stability. The experiments in the application address both the nature of functional specialization for the neuronal cytoskeleton and the cellular processes that affect them. These are genetic and biochemical adaptations of the cytoskeletal elements to specific biological requirements of neurons. Some result from programs initiated during differentiation of neurons and glia, while others represent responses to the local environment and are sensitive to subsequent changes in that environment. A novel biochemical specialization of the neuronal microtubule cytoskeleton has been identified that stabilizes axonal microtubules. The experiments in the first aim analyze the biochemistry of cold insoluble axonal tubulin and define physiological roles for stable axonal microtubule segments in neuronal function. The large size of many axons requires that the axonal cytoskeleton be influenced by the local microenvironment. Work in the last funding period on mutant strains of mice with defective myelination established that the myelinating glia profoundly influence both the composition and the local properties of the axonal cytoskeleton. The ext4nt to which the glial microenvironment can alter the organization and dynamics of the underlying axonal cytoskeleton will be continued to be examined in demyelinate and myelinated nerves. Experiments under aim 2 seek to define metabolic pathways for local modulation of the axonal cytoskeleton by the glial environment. The interaction between myelinating glia and axons in the PNS and CNS will be further characterized to determine the extent to which myelination sculpts the functional architecture of the axon. During the last funding period evidence accumulated that formation of compact myelin in the CNS was required for the maturation of the neuronal cytoskeleton. Experiments in aim 3 will identify pathways to myelinating glia modulate neuronal gene expression. These experiments will help identify mechanisms by which a specific molecular response of the axon to its environment is generated. The goal is to understand dynamics of the neuronal cytoskeleton that play critical roles in development, regeneration, and neuropathology.

描述(改编自申请人摘要)： 神经元细胞骨架是一组动态的、高度专业化的 在神经的许多方面起着关键作用的结构 系统，范围从神经元形态的产生和维护 涉及到定义神经元的功能域。为了履行这些职能， 细胞骨架的成分必须经过生化专门化才能 管住组织稳定。实验在应用中的应用 解决神经元功能特化的本质 细胞骨架和影响它们的细胞过程。这些是 细胞骨架元素的遗传和生化适应 神经元的特定生物学要求。一些结果来自于程序 起始于神经元和神经胶质细胞的分化，而其他的 代表对当地环境的响应，并对 该环境的后续变化。一种新型的生化制剂 神经元微管细胞骨架的特化 确定了稳定轴突微管的物质。实验中的实验 第一目的分析冷不溶性轴突微管蛋白的生物化学 确定稳定的轴突微管节段的生理作用 神经功能。许多轴突的大小要求轴突 细胞骨架受局部微环境的影响。在工作中工作 髓鞘缺陷小鼠突变株的最后资助期 证实髓鞘胶质细胞深刻地影响着 轴突细胞骨架的组成和局部特性。这个 神经胶质微环境可以改变组织结构的ext4nt 和潜在轴突细胞骨架的动力学将继续 在脱髓鞘和有髓神经中进行检查。AIM下的实验 2寻求确定局部调节轴突的代谢途径 细胞骨架受神经胶质环境的影响。两国之间的相互作用 三叉神经节和中枢神经系统的髓鞘胶质细胞和轴突将进一步 其特点是确定髓鞘形成雕刻的程度 轴突的功能结构。在上一个资助期内 越来越多的证据表明，在中枢神经系统形成致密的髓鞘是 是神经元细胞骨架成熟所必需的。实验 在Aim 3中，将确定髓鞘胶质细胞调节神经元的途径 基因表达。这些实验将通过以下方式帮助识别机制 轴突对其环境的特定分子反应是什么 已生成。其目标是了解神经元的动力学。 细胞骨架在发育、再生和发育过程中起关键作用 神经病理学。