Myelin Protein Polymorphism and Membrane Biogenesis

髓鞘蛋白多态性和膜生物发生

• 批准号: 7098745
• 负责人: JOHN H CARSON
• 金额: $ 26.9万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-04-01 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7098745
• 关键词: RNA; dynein ATPase; genetic polymorphism; genetic regulatory element; granule; intermolecular interaction; intracellular transport; kinesin; laboratory mouse; membrane biogenesis; microtubules; myelin basic proteins; oligodendroglia; tissue /cell culture

DESCRIPTION (provided by applicant): Intracellular RNA trafficking provides a mechanism to target gene expression to particular sub-cellular regions and to minimize ectopic expression elsewhere in the cell. Previous work has shown that eucaryotic RNAs are assembled into trafficking intermediates termed "granules." The direction and velocity of RNA granule trafficking is determined by cis-acting sequences in the RNA, trans-acting factors that bind to the RNA, and molecular motors (kinesin and dynein) that move RNA granules along microtubules. The central hypothesis of this proposal is that RNA trafficking is controlled by the balance of power between the opposing molecular motors kinesin and dynein in each granule. We will investigate 1) the mechanism of RNA granule assembly, 2) the movement of RNA granules along microtubules, 3) the regulation of kinesin and dynein activities by cis/trans trafficking determinants and 4) the steering of RNA trafficking in oligodendrocytes. The results will have significance for understanding the pathogenesis of demyelinating diseases such as multiple sclerosis that affect oligodendrocytes, the cellular and molecular mechanisms of learning and memory and synaptic plasticity in neurons, the control mechanisms for viral replication in HIV infected cells, and the molecular basis for some of the 82 different human diseases that involve intracellular trafficking.

描述（由申请人提供）： 细胞内RNA运输为靶向基因表达的机制提供了一种机制 特定的亚细胞区域，以最大程度地减少其他地方的异位表达 细胞。先前的工作表明，将桉树RNA组装到 被称为“颗粒”的贩运中间体。 RNA的方向和速度 颗粒运输是由RNA中的顺式作用序列确定的， 结合RNA和分子电动机的反式作用因子（动力学和动力学 沿微管移动RNA颗粒的动力蛋白。中心假设 该提议是RNA贩运受功率平衡控制 在每个颗粒中的相对分子电动机动力蛋白和动力蛋白之间。我们 将研究1）RNA颗粒组件的机理，2） 沿微管的RNA颗粒，3）驱动蛋白和动力蛋白的调节 顺式/反式贩运决定因素和4）RNA的转向 贩运少突胶质细胞。结果对 了解脱髓鞘疾病的发病机理，例如多种 影响少突胶质细胞，细胞和分子机制的硬化症 在神经元中学习，记忆和突触可塑性的控制 HIV感染细胞中病毒复制的机制和分子基础 对于涉及细胞内的82种不同的人类疾病中的一些 贩运。