力敏感突变揭示了dynein在无丝分裂进程中的非典型作用。

IF 7.4 1区 生物学 Q1 CELL BIOLOGY Journal of Cell Biology Pub Date : 2024-10-07 Epub Date: 2024-07-01 DOI:10.1083/jcb.202310022
David Salvador-Garcia, Li Jin, Andrew Hensley, Mert Gölcük, Emmanuel Gallaud, Sami Chaaban, Fillip Port, Alessio Vagnoni, Vicente José Planelles-Herrero, Mark A McClintock, Emmanuel Derivery, Andrew P Carter, Régis Giet, Mert Gür, Ahmet Yildiz, Simon L Bullock
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引用次数: 0

摘要

肌球蛋白马达在塑造微管网络和货物运输方面的作用多种多样,这使得对其功能的体内分析变得非常复杂。为了解决这个问题,我们在果蝇Dynein重链中产生了一系列错义突变。我们发现,与人类神经系统疾病相关的突变会导致一系列缺陷,包括神经元中的货物运输受损。我们还描述了一种新型微管结合域突变,它能特异性地阻断胚胎有丝分裂过程中的移行期-无丝分裂期转变。这种效应与动力蛋白在沉默纺锤体组装检查点中的典型作用无关。对纯化的动力蛋白复合物进行的光学捕获显示,这种突变只在负载条件下影响电机性能,全原子分子动力学模拟的结果也证明了这一发现的合理性。我们提出,dynein 在无丝分裂进程中具有一种新的功能,这种功能取决于它在特定的负载条件下运行。更广泛地说,我们的工作说明了如何通过操纵电机的机械特性来剖析其体内功能。
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A force-sensitive mutation reveals a non-canonical role for dynein in anaphase progression.

The diverse roles of the dynein motor in shaping microtubule networks and cargo transport complicate in vivo analysis of its functions significantly. To address this issue, we have generated a series of missense mutations in Drosophila Dynein heavy chain. We show that mutations associated with human neurological disease cause a range of defects, including impaired cargo trafficking in neurons. We also describe a novel microtubule-binding domain mutation that specifically blocks the metaphase-anaphase transition during mitosis in the embryo. This effect is independent from dynein's canonical role in silencing the spindle assembly checkpoint. Optical trapping of purified dynein complexes reveals that this mutation only compromises motor performance under load, a finding rationalized by the results of all-atom molecular dynamics simulations. We propose that dynein has a novel function in anaphase progression that depends on it operating in a specific load regime. More broadly, our work illustrates how in vivo functions of motors can be dissected by manipulating their mechanical properties.

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来源期刊
Journal of Cell Biology
Journal of Cell Biology 生物-细胞生物学
CiteScore
12.60
自引率
2.60%
发文量
213
审稿时长
1 months
期刊介绍: The Journal of Cell Biology (JCB) is a comprehensive journal dedicated to publishing original discoveries across all realms of cell biology. We invite papers presenting novel cellular or molecular advancements in various domains of basic cell biology, along with applied cell biology research in diverse systems such as immunology, neurobiology, metabolism, virology, developmental biology, and plant biology. We enthusiastically welcome submissions showcasing significant findings of interest to cell biologists, irrespective of the experimental approach.
期刊最新文献
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