Metaphase kinetochore movements are regulated by kinesin-8 motors and microtubule dynamic instability.
Metaphase kinetochore movements are regulated by kinesin-8 motors and microtubule dynamic instability.
复制标题
中期运动学运动受动力蛋白-8电动机和微管动态不稳定性调节。
DOI：
10.1091/mbc.e17-11-0667
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发表时间：
2018-06-01
影响因子：
3.3
通讯作者：
Tolic IM
中科院分区：
文献类型：
--
作者：
Klemm AH;Bosilj A;Gluncˇic M;Pavin N;Tolic IM
在中期，姐妹染色单体通过着丝点与染色体上的蛋白质复合体连接到从相反纺锤极延伸出来的微管上。动丝分体聚集在主轴的赤道平面上，并围绕它摆动，运动蛋白-8电机限制这些运动。然而，着丝点运动的物理机制尚不清楚。我们发现分裂酵母裂糖酵母（Schizosaccharomyces pombe）中的着丝点运动受激酶-8促进的微管突变、力诱导的拯救和微管动态不稳定性的调控。筛选结果表明，在所选择的马达中，只有激酶-8马达Klp5/Klp6是着丝点定心所必需的。动力蛋白8积聚在微管末端，在那里它会引发灾难。在野生型和klp5Δ细胞中，激光烧蚀纺锤体导致着丝点向完整的纺锤极运动，表明着丝点运动是由拉力驱动的。我们用朗格万描述微管动力学不稳定性的理论模型表明，着丝点定心需要激酶-8马达，而对力的敏感性是产生振荡所必需的。我们发现不规则的着丝点运动比规则的振荡发生在更大的参数范围内。因此，我们的工作为微管动态不稳定性的调节如何有助于着丝点的形成和伴随的纺锤体中心周围的运动提供了解释。
During metaphase, sister chromatids are connected to microtubules extending from the opposite spindle poles via kinetochores to protein complexes on the chromosome. Kinetochores congress to the equatorial plane of the spindle and oscillate around it, with kinesin-8 motors restricting these movements. Yet, the physical mechanism underlying kinetochore movements is unclear. We show that kinetochore movements in the fission yeast Schizosaccharomyces pombe are regulated by kinesin-8-promoted microtubule catastrophe, force-induced rescue, and microtubule dynamic instability. A candidate screen showed that among the selected motors only kinesin-8 motors Klp5/Klp6 are required for kinetochore centering. Kinesin-8 accumulates at the end of microtubules, where it promotes catastrophe. Laser ablation of the spindle resulted in kinetochore movement toward the intact spindle pole in wild-type and klp5Δ cells, suggesting that kinetochore movement is driven by pulling forces. Our theoretical model with Langevin description of microtubule dynamic instability shows that kinesin-8 motors are required for kinetochore centering, whereas sensitivity of rescue to force is necessary for the generation of oscillations. We found that irregular kinetochore movements occur for a broader range of parameters than regular oscillations. Thus, our work provides an explanation for how regulation of microtubule dynamic instability contributes to kinetochore congression and the accompanying movements around the spindle center.