CONTROL OF NEURONAL ORGANELLE TRANSPORT

神经细胞器运输的控制

• 批准号: 3413246
• 负责人: Peter J. Hollenbeck
• 金额: $ 16.83万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-01-01 至 1992-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3413246
• 关键词: axon; biological information processing; chick embryo; chromatography; cyclic AMP; cytoskeleton; developmental neurobiology; electrophoresis; membrane proteins; mitochondria; neurogenesis; neuronal transport; neurons; organelles; peripheral nervous system; phosphorylation; tissue /cell culture; western blottings

Although the rapid transport of neuronal organelles has been intensively studied using in vitro cell models, virtually nothing is known about how this phenomenon is controlled and coordinated in intact cells. One major aim of this study is to determine whether rapid organelle transport is modulated to deliver specific classes of organelles to regions of the neuron where they are needed. Using primary cultured chick neurons maintained in a culture system in which their elongation can be controlled, quantitative measurements of organelle transport will made to determine movement is coordinated with growth. The second major aim is to address how the direction of organelle movement is controlled, using conditions that influence the direction of transport in non-neuronal cells to probe intact and permeabilized neurons in culture. The third major aim of this study is to determine what role the mechanochemical ATPase kinesin plays in bidirectional rapid organelle transport. Specific antibodies directed against this enzyme will be introduced into cultured neurons in an effort to disrupt movement of a class of bidirectionally-transported organelles. Because it provides a metabolic link between the periphery of neurons and the site of synthesis in the cell body, rapid axonal transport is essential for the development and maintenance of all nerves; thus, the insight into its mechanism gained by the proposed research can be expected to contribute to our understanding of the development, defects, and diseases of the nervous system. In addition, since neuronal organelle transport must share many features in common with organelle traffic in other cell types, information acquired in this system should provide insight into many other systems of intracellular motility.

尽管神经元细胞器的快速运输已经很密集 使用体外细胞模型进行了研究，几乎对如何 该现象在完整的细胞中受到控制和协调。 一个主要 这项研究的目的是确定快速的细胞器传输是否是 调制以将特定类别的细胞器提供给 需要它们的神经元。 使用原发性培养的小鸡神经元 维持在其延伸的文化系统中 控制有机器传输的受控定量测量将对 确定运动与增长协调。 第二个主要目的是 解决了如何控制细胞器运动方向的方式 影响非神经元细胞转运方向的条件 在培养中探测完整和透化神经元。 第三个主要目标 这项研究是确定机械化学ATPase驱动蛋白的作用 在双向快速细胞器转运中发挥作用。 特定抗体 针对这种酶的针对这种酶将被引入 努力破坏一类双向传输的运动 细胞器。 因为它在外围之间提供了代谢联系 神经元和细胞体合成部位，快速轴突运输 对于所有神经的发育和维护至关重要。因此， 可以预期，可以洞悉拟议的研究所获得的机制 为我们理解发展，缺陷和 神经系统的疾病。 另外，由于神经元细胞器 运输必须共享许多与Organelle流量共同的功能 其他单元类型，此系统中获得的信息应提供 深入了解许多其他细胞内运动系统。