PROPERTIES OF AXONAL TUBULIN RELATED TO NEURONAL GROWTH

神经元细胞骨架的动力学特性影响神经元的许多方面。 神经系统，从神经元的产生和维持 形态学来定义神经元中的功能域。 这些都需要 细胞骨架元件对特定的 神经元的生物学需求。 有些是发起的计划的结果 在神经元和神经胶质细胞的分化过程中， 对当地环境的反应，并对随后的 这种环境的变化。 各种生化专业 神经元细胞骨架的结构已经被鉴定出来。 我们最近 证明了轴突微管蛋白的一种新的翻译后修饰， 可能在不溶性微管蛋白的生物发生中起重要作用。 实验 本申请试图表征不溶性微管蛋白并定义 稳定的轴突微管段在 神经生长和再生。 对震颤和颤抖小鼠的研究， 两种髓鞘形成缺陷的突变株， 轴突对不同微环境的局部反应。 的 神经胶质环境可以改变组织的程度， 下面的轴突细胞骨架的动力学将在 脱髓鞘和有髓鞘的神经。 髓鞘形成之间的相互作用 CNS和PNS中的神经胶质和轴突将被表征以确定 神经胶质细胞对轴突细胞骨架的局部调节程度 环境塑造了轴突的功能结构。 基于 我们证明PNS轴突的脱髓鞘会影响 轴突细胞骨架蛋白的组织和磷酸化。 我们 提出确定髓鞘形成改变的代谢途径， 细胞骨架磷酸化 这些实验将找出 轴突对其环境的特异性分子反应， 生成的. 我们的目标是为理解提供基础 发育、再生和神经病理学中的神经元动力学。

Dynamic properties of the neuronal cytoskeleton affect many aspects of the nervous system, ranging from generation and maintenance of neuronal morphologies to defining functional domains in a neuron. These require genetic and biochemical adaptations of cytoskeletal elements to specific biological requirements of neurons. Some result from programs initiated during differentiation of neurons and glia, while other represent responses to the local environment and are sensitive to subsequent changes in that environment. A variety of biochemical specializations of the neuronal cytoskeleton have been identified. We have recently demonstrated a novel posttranslation modification of axonal tubulin that may be important in the biogenesis of insoluble tubulin. Experiments in this application seek to characterize insoluble tubulin and to define the physiological roles played by stable axonal microtubule segments in neuronal growth and regeneration. Studies on Trembler and Shiverer mice, two mutant strains with deficient myelination, have begun to characterize the local responses of the axon to different microenvironments. The extent to which the glial environment can alter the organization and dynamics of the underlying axonal cytoskeleton will be examined in demyelinated and myelinated nerves. Interactions between myelinating glia and axons in the CNS and PNS will be characterized to determine the extent to which local modulation of the axonal cytoskeleton by the glial environment sculpts the functional architecture of the axon. Based on our demonstration that demyelination of PNS axons affects the organization and phosphorylation of axonal cytoskeletal proteins. We propose to identify metabolic pathways by which myelination alters cytoskeletal phosphorylation. These experiments will identify mechanisms by which a specific molecular response of the axon to its environment is generated. Our goal is to provide a foundation for understanding neuronal dynamics in development, regeneration, and neuropathology.