NEURITE OUTGROWTH FACTOR

神经突生长因子

• 批准号: 3399098
• 负责人: Louis French Reichardt
• 金额: $ 18.41万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-12-01 至 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3399098
• 关键词: axon; bioassay; cell differentiation; chickens; collagen; complementary DNA; cytoskeletal proteins; electron microscopy; enzyme mechanism; extracellular matrix; fibronectins; gene expression; genetic regulation; growth cones; growth factor receptors; high performance liquid chromatography; hybridomas; laboratory mouse; laboratory rabbit; laboratory rat; laminin; messenger RNA; molecular cloning; monoclonal antibody; neoplastic cell culture for noncancer research; nervous system regeneration; neuroanatomy; neurochemistry; neurogenesis; neuronal guidance; neurotrophic factors; nucleic acid sequence; pheochromocytoma; phosphorylation; protein structure function; radioassay; receptor binding

Neurons have been shown to interact with several different extracellular matrix glycoproteins, each of which is likely to help regulate axon growth and guidance during development and nerve regeneration. A family of extracellular matrix heterodimer receptors, named integrins, has been partially characterized and shown to be major mediators of neuronal interactions with the extracellular matrix. The characterization of two neuronal integrin receptors that mediate binding to laminin and collagen IV will be completed. Their structures, properties and function will be studied using the purified receptor heterodimers and subunit-specific antibodies, and by isolating and analyzing the sequences of cDNA clones. Using antibodies and cDNAs, the distributions of these receptor subunits in the nervous system will be analyzed. We will try to understand how they are regulated during development and nerve regeneration. Efforts will be made to identify factors that regulate their expression and activity. Using subunit-specific antibodies, we will try to identify some of the functions of these receptors in development and regeneration. Possible effects of NGF, a model trophic factor, on the expression, localization and function of these receptors will be examined with assays of subunit mRNA, protein, surface protein, phosphorylation and cytoskeletal associations. Using molecular biological analyses, we will attempt to identify and characterize domains of the receptor subunits required for NGF-dependent and NGF-independent neuronal process outgrowth.

神经元已被证明与几种不同的细胞外相互作用 基质糖蛋白，每种都可能有助于调节轴突生长 以及发育和神经再生过程中的指导。一个家庭 细胞外基质异二聚体受体，称为整合素，已被 部分表征并显示为神经元的主要介质 与细胞外基质的相互作用。两个人的性格特点 介导与层粘连蛋白和 IV 型胶原蛋白结合的神经元整合素受体 将完成。它们的结构、性质和功能将是 使用纯化的受体异二聚体和亚基特异性进行研究 抗体，并通过分离和分析 cDNA 克隆的序列。 使用抗体和 cDNA，这些受体亚基的分布 将分析神经系统。我们将尝试了解他们的情况 在发育和神经再生过程中受到调节。将会做出努力 以确定调节其表达和活性的因素。使用 亚基特异性抗体，我们将尝试识别一些功能 这些受体的发育和再生。可能的影响 NGF，一种模型营养因子，关于表达、定位和功能 这些受体的检测将通过亚基 mRNA、蛋白质、 表面蛋白、磷酸化和细胞骨架关联。使用 分子生物学分析，我们将尝试识别和表征 NGF 依赖所需的受体亚基结构域 不依赖 NGF 的神经元过程的生长。