OLIGODENDROCYTE ONTOGENY AND DIFFERENTIATION

少突胶质细胞个体发育和分化

• 批准号: 6825711
• 负责人: ELISA M BARBARESE
• 金额: $ 25.38万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-01-05 至 2007-05-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6825711
• 关键词: cell differentiation; confocal scanning microscopy; developmental neurobiology; heterogeneous nuclear ribonucleoprotein; immunocytochemistry; immunoprecipitation; intracellular transport; laboratory mouse; messenger RNA; microinjections; myelin; myelin basic proteins; myelination; neuronal transport; oligodendroglia; protein biosynthesis; protein signal sequence; protein transport; tissue /cell culture; transcription factor; yeast two hybrid system

DESCRIPTION (From the Applicant's Abstract): The major function of the oligodendrocyte in the CNS is to produce myelin, the membrane sheath that envelops axons and is necessary for saltatory conduction. Our long term goal is to elucidate the process of myelination and its regulation. Myelin basic protein (MBP), a major structural component of the sheath, is essential for the formation of myelin. MBP is synthesized at its site of assembly in the myelin membrane. This is accomplished by transport of MBP mRNA from the nucleus to the cell body and down the cell processes and into the myelin sheath, followed by anchoring and translation. The short term goal of our research efforts is to elucidate this trafficking pathway. This will be accomplished by: Characterizing the expression of heterogeneous nuclear ribonucleoprotein (hnRNP) A2, the essential trans-acting factor that recognizes the signal sequence for transport present in MBP mRNA; identifying other constituents of the MBP mRNA trafficking system and determining their role; characterizing the conditions under which MBP mRNA trafficking is blocked or enhanced, and delineating the steps in MBP mRNA translocation from the nucleus to the myelin membrane and pattern of regulation. Microinjection of live cell in culture, confocal microscopy, immunocytochemistry, Western blot, yeast two-hybrid system, co-immunoprecipitation and subcellular fractionation procedures will be used. Hypomyelination and demyelination have severe neurological consequences. Understanding the mechanism of mRNA trafficking is the first step in understanding how myelin is made a repaired throughout the life of an individual. This knowledge should lead to therapies, immunochemical or pharmaceutical for patients afflicted with demyelinating diseases of the CNS and PNS such as multiple sclerosis, Charcot-Marie-Tooth disease and Guillain-Barre syndrome, and for patients with demyelinating conditions following therapeutic irradiation and chemotherapy or viral infections.

描述（摘自申请人的摘要）： 中枢神经系统中的少突胶质细胞是产生髓磷脂，即膜鞘 信封轴突，对于盐酸传导是必​​需的。我们的长期目标是 阐明髓鞘及其调节的过程。髓线碱 蛋白质（MBP）是鞘的主要结构成分，对于 髓磷脂的形成。 MBP在其髓鞘的组装位置合成 膜。这是通过将MBP mRNA从细胞核传输到 细胞体并沿细胞过程和髓鞘鞘中的细胞过程，然后 锚定和翻译。我们研究工作的短期目标是 阐明这一贩运途径。这将通过： 表征异质核核糖核蛋白的表达 （HNRNP）A2，识别信号的基本跨性别因子 MBP mRNA中存在的运输序列；确定其他成分 MBP mRNA贩运系统并确定其作用；表征 MBP mRNA贩运被阻止或增强的条件，以及 描述从细胞核到髓磷脂的MBP mRNA易位的步骤 膜和调节模式。在培养物中的活细胞显微注射， 共聚焦显微镜，免疫细胞化学，蛋白质印迹，酵母两杂交 系统，免疫沉淀和亚细胞分级程序将是 用过的。 低切髓和脱髓鞘具有严重的神经系统后果。 了解mRNA贩运的机制是第一步 了解如何在整个生命的一生中修复髓鞘 个人。这些知识应导致疗法，免疫化学或 患有CNS脱髓鞘疾病的患者的药物 和PN，例如多发性硬化症，charcot-marie-tooth疾病和 GUILLAIN-BARRE综合征，适用于脱髓鞘状况的患者 治疗辐射和化学疗法或病毒感染后。