PROPERTIES OF AXONAL TUBULIN RELATED TO NEURONAL GROWTH

这里描述的研究的长期目标是理解 神经细胞的分子机制和特性 神经元发育过程中必不可少的细胞骨架 发展、老化和再生。微管蛋白是一种主要的蛋白质 脊椎动物的大脑和神经元的主要组成部分 细胞骨架。已知的大脑微管通常是 异质，但功能意义不佳 明白了。在这项提案中，一种特殊形式的微管蛋白和 与轴突相关的微管的特征是 生化和免疫化学方法。这一分析是 对于了解的组成和属性 轴突细胞骨架。先前的研究表明，大部分 轴突微管蛋白不溶于水，以稳定结构域的形式存在 在轴突微管中。不溶性微管蛋白在人体内的分布 神经元和非神经元细胞，在亚细胞域和在 微管将通过免疫组织化学和 放射免疫分析。不溶性微管蛋白在调节血管内皮细胞生长中的作用 轴突细胞骨架的组织和稳定性将是 调查过了。因为稳定结构域的存在将 影响神经元细胞骨架的动力学，改变 发育、衰老和再生过程中的轴突细胞骨架 都将被详细检查。可能的监管机制 神经元细胞骨架的原位特性，包括 髓鞘形成和神经元-雪旺细胞的相互作用 将对神经元细胞骨架的调节器进行评估。这些 研究将使我们更好地理解 微管蛋白、微管和神经元细胞骨架在 神经元的发育和再生以及鉴定 调控黄曲霉毒素性质的分子机制 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.