NOVEL NERVOUS SYSTEM GLYCOPROTEINS IN AXONAL GROWTH

目的是了解轴突背后的分子机制。 外延生长。人们普遍认为，原子核表面的分子 生长中的轴突与环境中的其他分子相互作用， 这些分子相互作用对于实现正常的 神经元连接。在我们实验室，一种单抗4D7已经 最近制备的一种识别一组糖蛋白的药物 显然与轴突生长有关。我们提出了一组全面的 这些4D7糖蛋白的研究旨在回答 它们的结构与功能的关系。这些研究 包括：1)碳水化合物和多肽部分的化学 分子。2)分析了这些基因的表达调控 糖蛋白及其与细胞黏附的关系 分子，以及3)这些蛋白质的功能特性的研究， 特别是它们在轴突生长和轴突再生中的作用。 哺乳动物神经发育过程中这些糖蛋白的分析 该系统可能有助于我们理解轴突生长的机制。 正常人脑的发育。在表达上是否有任何异常 这些蛋白质可能会产生严重的发育后果。 因此，这个项目很可能会提供相关的信息 为未来智力低下的研究做准备。也将为我们的 关于神经再生的知识，这可能对 未来周围神经损伤的治疗。 对于这些小说，我们提出了一个多层面的分析方法 糖蛋白。免疫学和细胞培养方法的使用占主导地位。 这些项目。将使用可用的单抗。 用于免疫亲和层析纯化蛋白质。这些 抗体也将被广泛用于免疫细胞化学研究， 光镜和电子显微镜水平。这些抗体将用于 原代培养系统，以阐明细胞的功能特性 糖蛋白。此外，克隆抗体的生产 针对每个4D7免疫反应蛋白计划提供 开展这些项目所需的额外探测。

The objectives are to understand the molecular mechanisms underlying axonal outgrowth. It is generally believed that molecules on the surface of growing axons interact with other molecules in their environment, and that these molecular interactions are essential for the achievement of normal neuronal connections. In our laboratory, a monoclonal antibody 4D7 has recently been prepared which recognizes a group of glycoproteins that are apparently involved in axonal growth. We propose a comprehensive group of studies of these 4D7 glycoproteins which are designed to answer the relationship between their structures and their functions. These studies include: 1) chemistry of the carbohydrate and peptide portions of the molecules. 2) analysis of the regulation of expression of these glycoproteins, and their relationship to previously described cell adhesion molecules, and 3) a study of the functional properties of these proteins, particularly their role in neurite outgrowth and axon regeneration. Analysis of these glycoproteins in the development of the mammalian nervous system may help us to understand the mechanisms of axonal growth in development of normal human brain. Any abnormalities in the expression of these proteins would likely have severe developmental consequences. Therefore, it is likely that this project will provide relevant information for future studies in mental retardation. And will also contribute to our knowledge of nerve regeneration, which could have positive implications for future treatment of peripheral nerve injuries. A multi-faceted approach is proposed for the analysis of these novel glycoproteins. The use of immunological and cell culture methods dominate these projects. Monoclonal antibodies, which are available, will be used for immunoaffinity chromatographic purification of proteins. These antibodies will also be used extensively for immunocytochemical studies at the light and electron microscopic levels. The antibodies will be used in primary culture systems to elucidate the functional properties of the glycoproteins. In addition, the production of monoclonal antibodies specific for each 4D7-immunoreactive proteins is planned to provide additional probes to carry out these projects.