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: 10626768
• 负责人: Vladimir I Gelfand
• 金额: $ 91.64万
• 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/10626768
• 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; Sorting; 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.

项目概要 该项目的总体目标是了解微管马达驱动蛋白和动力蛋白如何组织 间期细胞中的细胞骨架，从而驱动细胞极化。我们小组最近发现 主要运动蛋白、驱动蛋白-1 和细胞质动力蛋白，此外还可以移动多种类型的货物 微管有一个新功能：它们定义了两类微管的分布和动态行为 间期细胞中的细胞骨架丝、微管和中间丝。我们已经证明两者 微管和中间丝被运动蛋白作为聚合物运输。此运输 定义了细胞骨架的一般组织，以及细胞极性。三种生物学模型 本提案中研究的极化是：（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分类 偏振阵列； (ii) 果蝇卵母细胞，其中微管通过驱动蛋白-1 的运输驱动卵母细胞的旋转 细胞质用于定位对发育胚胎至关重要的极性决定因素，以及细胞质动力蛋白 将微管运输到保育细胞中以及从保育细胞运输到卵母细胞，以及（iii）运输中间体 哺乳动物细胞中沿着微管的细丝，这对于定向细胞迁移很重要。

项目成果

Nanoscale architect: Illuminating the key organizer of the fruit fly's sensory world.

纳米级建筑师：阐明果蝇感官世界的关键组织者。

• DOI: 10.1083/jcb.202308028
• 发表时间: 2023
• 期刊: The Journal of cell biology
• 作者: Lu,Wen;Gelfand,VladimirI
• 通讯作者: Gelfand,VladimirI

Ataxin-2 is essential for cytoskeletal dynamics and neurodevelopment in Drosophila.

• DOI: 10.1016/j.isci.2021.103536
• 发表时间: 2022-01-21
• 期刊: iScience
• 影响因子: 5.8
• 作者: Del Castillo U;Norkett R;Lu W;Serpinskaya A;Gelfand VI
• 通讯作者: Gelfand VI

Repurposing Kinetochore Microtubule Attachment Machinery in Neurodevelopment.

• DOI: 10.1016/j.devcel.2019.03.004
• 发表时间: 2019-03
• 期刊: Developmental cell
• 影响因子: 11.8
• 作者: R. Norkett;Wen Lu;Vladimir Gelfand

Tissue architecture: Two kinesins collaborate in building basement membrane.

• DOI: 10.1016/j.cub.2022.01.006
• 发表时间: 2022-02-28
• 期刊: CURRENT BIOLOGY
• 影响因子: 9.2
• 作者: Lu, Wen;Gelfand, Vladimir, I
• 通讯作者: Gelfand, Vladimir, I

Ser/Thr kinase Trc controls neurite outgrowth in Drosophila by modulating microtubule-microtubule sliding.

Ser/Thr 激酶 Trc 通过调节微管-微管滑动来控制果蝇中的神经突生长。

• DOI: 10.7554/elife.52009
• 发表时间: 2020
• 期刊: eLife
• 影响因子: 7.7
• 作者: Norkett,Rosalind;DelCastillo,Urko;Lu,Wen;Gelfand,VladimirI
• 通讯作者: Gelfand,VladimirI