NOVEL NERVOUS SYSTEM GLYCOPROTEINS IN AXONAL GROWTH

轴突生长中的新型神经系统糖蛋白

• 批准号: 3409606
• 负责人: MIYUKI YAMAMOTO
• 金额: $ 16.97万
• 依托单位: EUNICE KENNEDY SHRIVER CTR MTL RETARDATN
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-04-01 至 1990-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3409606
• 关键词: affinity chromatography; axon; binding proteins; brain cell; brain stem; cell cell interaction; developmental genetics; dorsal root; electron microscopy; embryo /fetus culture; extracellular matrix; gas chromatography; glycoproteins; high performance liquid chromatography; immunochemistry; laboratory mouse; laboratory rat; mass spectrometry; membrane proteins; mental retardation; monoclonal antibody; nervous system regeneration; neurogenesis; neuronal guidance; peripheral nervous system; protein structure; surface antigens; tissue /cell culture

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.

目的是了解轴突的分子机制 生长出来的。 一般认为，表面分子 生长的轴突与环境中的其他分子相互作用，并且 这些分子相互作用对于实现正常功能至关重要 神经元连接。 在我们的实验室，单克隆抗体 4D7 具有 最近制备的可识别一组糖蛋白 显然参与轴突生长。 我们提出了一个全面的小组 对这些 4D7 糖蛋白的研究旨在回答 它们的结构和功能之间的关系。 这些研究 包括：1）碳水化合物和肽部分的化学性质 分子。 2）这些表达调控的分析 糖蛋白及其与先前描述的细胞粘附的关系 分子，以及 3) 对这些蛋白质功能特性的研究， 特别是它们在神经突生长和轴突再生中的作用。 分析哺乳动物神经发育中的这些糖蛋白 系统可以帮助我们了解轴突生长的机制 人类大脑的正常发育。 任何表达异常 这些蛋白质可能会产生严重的发育后果。 因此，该项目很可能会提供相关信息 为未来的精神发育迟滞研究。 也将为我们做出贡献 神经再生的知识，这可能对神经再生产生积极影响 周围神经损伤的未来治疗。 提出了一种多方面的方法来分析这些新颖的 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。 将使用现有的单克隆抗体 用于蛋白质的免疫亲和层析纯化。 这些 抗体也将广泛用于免疫细胞化学研究 光和电子显微镜水平。 该抗体将用于 原代培养系统以阐明其功能特性 糖蛋白。 此外，单克隆抗体的生产 计划提供针对每种 4D7 免疫反应蛋白的特异性 进行这些项目的额外调查。