Milton and the Transport of Mitochondria

弥尔顿和线粒体的运输

• 批准号: 7117684
• 负责人: Thomas L. Schwarz
• 金额: $ 28.88万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-20 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7117684
• 关键词: Drosophilidae; RNA splicing; axon; cell line; chemical kinetics; cytoskeleton; dendrites; electron microscopy; embryo /fetus; fluorescence microscopy; gene expression; genetic regulation; glycosylation; intermolecular interaction; kinesin; larva; mitochondria; nerve /myelin protein; neuronal transport; neurons; neuroregulation; phosphorylation; protein localization; protein structure function; video microscopy

DESCRIPTION (provided by applicant): Motor proteins move organelles within the cytoplasm of cells and thereby contribute to the appropriate distribution of those organelles. The motors involved, including members of the kinesin family, are of considerable interest from the cell biological point of view: how do motors couple to their appropriate cargos?; how do they direct those cargos to particular locations?; how is their activity regulated?; how is the proper distribution of the organelle achieved and maintained? The proper distribution of an organelle can pose a complex problem for a cell. Defects in this process can cause peripheral neuropathies and have been implicated in some neurodegenerative diseases. Mitochondria are highly mobile organelles. They must distribute themselves within cells so as to be able to supply sufficient energy to each part of a cell to match the needs of that part. The movement of mitochondria up and down axons and dendrites of neurons is one of the most dramatic examples of mitochondrial transport. In a Drosophila mutant called milton, mitochondria are completely absent from nerve axons and terminals. The protein encoded by the milton gene is found on mitochondria and is associated with the motor protein kinesin. The present proposal seeks to understand the role of Milton in the transport of mitchondria within neurons and other cells. The first aim, involving primarily fluorescent and video microscopy, seeks to determine what forms of transport require Milton and to determine if Milton is on all mitochondria or only those that are undergoing transport. The subsequent aims probe the mechanism of Milton action, primarily through biochemical studies. They inquire how Milton is localized to mitochondria, how Milton interacts with kinesin, and whether Milton serves as an adaptor that links kinesin to the mitochondrion. In the process, the proposal also examines the alternative splicing of the Milton gene and the potential regulatory role of post-translational modifications of Milton.

描述（由申请人提供）：运动蛋白在细胞的细胞质内移动细胞器，从而有助于这些细胞器的适当分布。从细胞生物学的角度来看，涉及的电动机，包括动力素家族的成员，引起了人们的极大兴趣：电动机如何与适当的货物相对。他们如何将这些货物引导到特定位置？他们的活动如何受到监管？细胞器的正确分布如何实现和维护？细胞器的适当分布可能会给细胞带来一个复杂的问题。在此过程中的缺陷会引起周围神经病，并与某些神经退行性疾病有关。线粒体是高度移动的细胞器。他们必须在细胞中分配自己，以便能够为细胞的每个部分提供足够的能量，以符合该部分的需求。线粒体上下轴突和神经元树突的运动是线粒体转运的最戏剧性的例子之一。在称为米尔顿的果蝇突变体中，神经轴突和末端完全不存在线粒体。 米尔顿基因编码的蛋白质在线粒体上发现，与运动蛋白驱动蛋白有关。本提案旨在了解米尔顿在神经元和其他细胞中米孔氏菌运输中的作用。主要涉及荧光和视频显微镜的第一个目标是旨在确定哪种运输形式需要米尔顿，并确定米尔顿是否在所有线粒体上或仅在运输的线粒体上。随后的目的是探测米尔顿作用的机理，主要是通过生化研究。他们询问米尔顿是如何将米尔顿本地化的，米尔顿如何与运动蛋白互动，以及米尔顿是否是将驱动蛋白与线粒体联系起来的适配器。在此过程中，该提案还研究了米尔顿基因的替代剪接以及米尔顿翻译后修饰的潜在调节作用。