Kif18A and chromokinesins confine centromere movements via microtubule growth suppression and spatial control of kinetochore tension.

Kif18A and chromokinesins confine centromere movements via microtubule growth suppression and spatial control of kinetochore tension.
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KIF18A和染色体通过微管生长抑制和动力学张力的空间控制来限制着丝粒运动。

DOI:
10.1016/j.devcel.2012.02.013
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发表时间:
2012-05-15
期刊:
影响因子:
11.8
通讯作者:
Wordeman, Linda
Wordeman, Linda
中科院分区:
生物学1区
文献类型:
--
作者:
Stumpff, Jason;Wagenbach, Michael;Franck, Andrew;Asbury, Charles L.;Wordeman, Linda

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染色体在中期平板上的排列是后生动物细胞分裂的标志,但控制这一过程的机制仍然不明确。在这里,我们使用定量活细胞成像和重组动态微管分析相结合的方法来研究有丝分裂着丝粒运动的分子控制。我们证实Kif18A(Kinesin-8)通过以浓度依赖的方式直接促进微管停顿来减弱着丝粒运动。这一活动提供了将着丝粒运动限制在纺锤体中区的主要机制。此外,极地抛射通过对着丝粒张力和着丝粒切换率的位置依赖调节,迫使染色体在空间上受到限制。我们证明了极地射出力被嗜铬激动素拮抗地调制。这些推力依赖于Kid(Kinesin-10)的活性,并被Kif4A(Kinesin-4)所拮抗,Kif4A的作用是直接抑制微管的生长。这些数据支持Kif18A和极射出力通过动粒-微管动力学的空间控制协同促进着丝粒排列的模型。
Alignment of chromosomes at the metaphase plate is a signature of cell division in metazoan cells, yet the mechanisms controlling this process remain ambiguous. Here we use a combination of quantitative live cell imaging and reconstituted dynamic microtubule assays to investigate the molecular control of mitotic centromere movements. We establish that Kif18A (kinesin-8) attenuates centromere movement by directly promoting microtubule pausing in a concentration-dependent manner. This activity provides the dominant mechanism for restricting centromere movement to the spindle midzone. Furthermore, polar ejection forces spatially confine chromosomes via position-dependent regulation of kinetochore tension and centromere switch rates. We demonstrate that polar ejection forces are antagonistically modulated by chromokinesins. These pushing forces depend on Kid (kinesin-10) activity and are antagonized by Kif4A (kinesin-4), which functions to directly suppress microtubule growth. These data support a model in which Kif18A and polar ejection forces synergistically promote centromere alignment via spatial control of kinetochore-microtubule dynamics.
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