Microtubule motors, cytoskeletal organization and cell polarity

微管马达、细胞骨架组织和细胞极性

• 批准号: 10406364
• 负责人: Vladimir I Gelfand
• 金额: $ 87.5万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-07 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10406364
• 关键词: Actins; Axon; Behavior; Biological Models; Cell Polarity; Cells; Cytoplasm; Cytoskeletal Filaments; Cytoskeletal Modeling; Cytoskeleton; Dendrites; Development; Drosophila genus; Dynein ATPase; Elements; Embryo; Goals; Intermediate Filaments; Interphase Cell; Kinesin; Mammalian Cell; Microtubules; Molecular Motors; Motor; Movement; Neurodegenerative Disorders; Neurons; Nurses; Oocytes; Organism; Polymers; Positioning Attribute; Process; Proteins; RNA; Rotation; cell motility; developmental disease; new therapeutic target; polarized cell

Project Summary The overall goal of this project is to understand how microtubule motors kinesin and dynein organize cytoskeleton in interphase cells and, as a result, drive cell polarization. Our group recently discovered that major motor proteins, kinesin-1 and cytoplasmic dyneins, in addition to moving many types of cargoes along microtubules, have a new function: they define the distribution and dynamic behavior of two classes of cytoskeletal filaments, microtubules and intermediate filaments in interphase cells. We have shown that both microtubules and intermediate filaments are being transported as polymers by motor proteins. This transport defines general organization of the cytoskeleton, and, as a result, cell polarity. Three biological models of polarization studied in this proposal are: (i) Drosophila neurons, where movement of microtubules by kinesin-1 drives initial extension of axons and dendrites, and cortical dynein sorts axonal microtubules into uniformly polarized arrays; (ii) Drosophila oocytes, where transport of microtubules by kinesin-1 drives rotation of cytoplasm for localization of polarity determinants critical for the developing embryo, and cytoplasmic dynein transports microtubules in nurse cells and from nurse cells to the oocyte and (iii) transport of intermediate filaments along microtubules in mammalian cells, which is important for directed cell migration.

项目摘要 该项目的总体目标是了解微管电动机动力蛋白和Dynein如何组织 相间细胞中的细胞骨架，结果驱动细胞极化。我们的小组最近发现 主要运动蛋白，驱动蛋白1和细胞质动力蛋白，除了将许多类型的货物移动 微管，具有新功能：它们定义了两类的分布和动态行为 相间细胞中的细胞骨架细丝，微管和中间丝。我们已经证明了这两个 微管和中间丝通过运动蛋白作为聚合物传输。这辆运输 定义细胞骨架的一般组织，并因此是细胞极性。三种生物模型 该提案中研究的极化是：（i）果蝇神经元，微管的运动通过驱动蛋白1 将轴突和树突的初始延伸驱动，以及皮质动力蛋白将轴突微管分类成均匀的 极化阵列； （ii）果蝇卵母细胞，其中微管通过驱动蛋白1驱动旋转 细胞质用于定位极性决定因素对发育中的胚胎至关重要，细胞质动力蛋白 在护士细胞中运输微管，从护士细胞到卵母细胞和（iii）中间体的运输 沿哺乳动物细胞中微管的细丝，这对于定向细胞迁移很重要。