MEMBRANE FACTORS REGULATING TRANSMITTER EXPRESSION

调节递质表达的膜因子

• 批准号: 3779102
• 负责人: IRA B BLACK
• 金额: --
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3779102
• 关键词: SDS polyacrylamide gel electrophoresis; antiserum; cell membrane; complementary DNA; crosslink; developmental neurobiology; gene expression; genetic regulation; growth factor receptors; immunocytochemistry; in situ hybridization; laboratory rat; mixed tissue /cell culture; molecular site; neurotransmitters; neurotrophic factors; northern blottings; radioimmunoassay; radiotracer; receptor binding; tissue /cell culture

The Development of the nervous system is dependent on a host of proteins which influence a variety of differentiative events. We have discovered one such factor which appears to regulate several developmental processes including mitosis of embryonic neuroblasts, differentiation of neurotransmitter traits in post-mitotic neurons, and expression of the trophic factor, nerve growth factor NGF, in glial cells of the central nervous system. This membrane-derived differentiating factor (MDF), extracted from rat spinal cords, has recently been purified to homogeneity. The goal of this project is to determine the critical role of MDF during development and to elucidate the molecular mechanisms underlying neuronal responses to the factor. Using amino acid sequence data from the purified factor, we plan to clone and sequence the cDNA that encodes MDF. This cDNA as well as antisera generated against MDF will be used to characterize its distribution and ontogeny by immunohistochemistry, and Northern blots to determine potential roles and sites of action. The antisera will also be used to disrupt the normal function of MDF to examine its role in vivo. To begin defining the molecular mechanisms involved in the various activities, 125I-MDF binding assays will be employed to identify and characterize its specific receptor(s). Our studies may provide information concerning the molecular basis for such congenital neurologic diseases as Familial Dysautonomia and dystonia musculorum deformans. Investigation of novel factors such as MDF and underlying molecular mechanisms may provide an entirely new class of therapeutic agents to treat birth defects.

神经系统的发展取决于许多蛋白质 会影响各种区分事件。 我们发现了 这样的因素似乎可以调节几种发展 包括胚胎神经细胞有丝分裂的过程，分化 神经递质特征在有丝分裂后神经元中，并表达 营养因子，神经生长因子NGF，中央的神经胶质细胞 神经系统。 该膜衍生的区分因子（MDF）， 从大鼠脊髓提取，最近已纯化为 同质性。 该项目的目的是确定关键作用 MDF在开发过程中的MDF并阐明分子机制 对因素的基本神经元反应。 使用氨基酸序列 来自纯化因子的数据，我们计划克隆并对cDNA进行测序 这编码MDF。 该cDNA以及针对MDF产生的抗血清 将用于表征其分布和个体发育 免疫组织化学和北印迹以确定潜在的作用 和行动部位。 安排也将被用来破坏 MDF检查其在体内的作用的正常功能。 开始定义 各种活动涉及的分子机制，125i-MDF 将使用约束分析来识别和表征其 特定受体。 我们的研究可能会提供有关的信息 这种先天性神经系统疾病的分子基础 功能障碍和肌张力障碍肌肉畸形。 小说的调查 MDF和基础分子机制等因素可能会提供 全新的治疗剂治疗先天缺陷。