PROPERTIES OF AXONAL TUBULIN RELATED TO NEURONAL GROWTH

这里描述的研究的长期目标是了解 神经元的分子机制和特性 细胞骨架对神经元的发育过程至关重要 发育老化和再生 微管蛋白是一种主要的蛋白质 是脊椎动物大脑神经元的主要组成部分 细胞骨架 已知脑微管通常 异质性，但功能意义不佳 明白 在这项提议中，一种特殊形式的微管蛋白和 与轴突相关的微管具有以下特征： 生物化学和免疫化学方法。 这种分析是 重要的是了解的组成和性质的 轴突细胞骨架 以前的研究表明， 轴突微管蛋白是不溶性的，以稳定结构域的形式存在 在轴突微管中。 不溶性微管蛋白的分布 神经元和非神经元细胞，在亚细胞域， 将通过免疫组织化学分析微管， 放射免疫测定 不溶性微管蛋白在调节细胞凋亡中的作用 轴突细胞骨架的组织和稳定性将是 研究了 由于稳定域的存在 影响神经元细胞骨架的动力学， 发育、衰老和再生过程中的轴突细胞骨架 都要详细检查 可能的调节机制 原位神经元细胞骨架的特性，包括 髓鞘形成和神经元-许旺细胞相互作用 将评估神经元细胞骨架的调节剂。 这些 研究将提供一个更好的了解的作用， 微管蛋白、微管和神经元细胞骨架在神经元的细胞骨架中起着重要作用。 神经元的发育和再生以及识别 参与调节的分子机制， 神经元微管

The long range goal of the studies described here is to understand the molecular mechanisms and properties of the neuronal cytoskeleton that are essential to the process of neuronal development, aging, and regeneration. Tubulin is a major protein of vertebrate brain and a primary constituent of the neuronal cytoskeleton. Brain microtubules are known to be usually heterogeneous, but the functional significance is not well understood. In this proposal, a specialized form of tubulin and microtubules associated with the axon are characterized by both biochemical and immunochemical methods. This analysis is important for understanding the composition and properties of the axonal cytoskeleton. Previous work has shown that the bulk of axonal tubulin is insoluble and exists in the form of stable domains in axonal microtubules. The distribution of insoluble tubulin in neurons and nonneuronal cells, in subcellular domains, and within microtubules will be analyzed by immunohistochemistry and radioimmunoassays. The role of insoluble tubulin in regulating the organization and stability of the axonal cytoskeleton will be investigated. Since the presence of the stable domains would affect the dynamics of the neuronal cytoskeleton, changes in the axonal cytoskeleton during development, aging, and regeneration are to be examined in detail. Possible mechanisms for regulating properties of the neuronal cytoskeleton in situ, including myelination and neuron-Schwann cell interactions as possible modulators of the neuronal cytoskeleton will be evaluated. These studies will provide a better understanding of the roles that tubulin, microtubules, and the neuronal cytoskeleton play in the development and regeneration of neurons as well as identifying the molecular mechanisms involved in regulating the properties of neuronal microtubules.