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.

项目总结

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