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 这个项目的总体目标是了解微管马达驱动蛋白和动力蛋白是如何组织的 在间期细胞中的细胞骨架，并因此驱动细胞极化。我们小组最近发现， 主要的马达蛋白，驱动蛋白-1和细胞质动力蛋白，除了移动许多类型的货物沿着 微管，有一个新的功能：他们定义的分布和动态行为的两类 间期细胞中的细胞骨架丝、微管和中间丝。我们已经证明， 微管和中间丝作为聚合物被马达蛋白运输。此传输 定义了细胞骨架的一般组织，并因此定义了细胞极性。三种生物模型 在这个提议中研究的极化是：（i）果蝇神经元，其中微管的运动由驱动蛋白-1 驱动轴突和树突的初始延伸，皮质动力蛋白将轴突微管均匀地分类成 极化阵列;（ii）果蝇卵母细胞，其中驱动蛋白-1的微管运输驱动微管的旋转。 细胞质定位极性决定因素的关键发展胚胎，和细胞质动力蛋白 运输保育细胞中的微管和从保育细胞到卵母细胞和（iii）运输中间体 在哺乳动物细胞中沿着微管的纤维，这对于定向细胞迁移是重要的。