Pivoting of microtubules around the spindle pole accelerates kinetochore capture

Pivoting of microtubules around the spindle pole accelerates kinetochore capture
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DOI:
10.1038/ncb2640
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发表时间:
2013-01-01
影响因子:
21.3
通讯作者:
Tolic-Norrelykke, Iva M.
Tolic-Norrelykke, Iva M.
中科院分区:
生物学1区
文献类型:
--
作者:
Kalinina, Iana;Nandi, Amitabha;Tolic-Norrelykke, Iva M.

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在细胞分裂过程中,纺锤体微管通过着丝点(染色体上的蛋白质复合物)附着在染色体上(1)。核心问题是微管如何找到着丝点。根据被称为“搜索-捕获”的开创性想法,许多微管从中心体向各个方向生长,并偶然捕获着丝点(2-4)。通过微管偏向于着丝点生长(5,6)、微管在着丝点成核(7-9)和纺锤体微管成核(10,11)、着丝点运动(9)或这些过程的组合(12-14),可以提高搜索和捕获的效率。这里我们展示了在分裂酵母中,着丝点被围绕纺锤极旋转的微管捕获,而不是朝着着丝点生长。这种微管的旋转运动是随机的,与atp驱动的运动活动无关。通过引入理论模型,我们证明了微管和着丝点的随机运动足以解释着丝点捕获的过程。我们的理论预测,捕获的速度主要取决于微管旋转的速度,通过加速和减慢微管旋转的实验证实了这一点。因此,旋转运动允许微管在寻找着丝点等目标时横向探索空间。
During cell division, spindle microtubules attach to chromosomes through kinetochores, protein complexes on the chromosome(1). The central question is how microtubules find kinetochores. According to the pioneering idea termed search-and-capture, numerous microtubules grow from a centrosome in all directions and by chance capture kinetochores(2-4). The efficiency of search-and-capture can be improved by a bias in microtubule growth towards the kinetochores(5,6), by nucleation of microtubules at the kinetochores(7-9) and at spindle microtubules(10,11), by kinetochore movement(9), or by a combination of these processes(12-14). Here we show in fission yeast that kinetochores are captured by microtubules pivoting around the spindle pole, instead of growing towards the kinetochores. This pivoting motion of microtubules is random and independent of ATP-driven motor activity. By introducing a theoretical model, we show that the measured random movement of microtubules and kinetochores is sufficient to explain the process of kinetochore capture. Our theory predicts that the speed of capture depends mainly on how fast microtubules pivot, which was confirmed experimentally by speeding up and slowing down microtubule pivoting. Thus, pivoting motion allows microtubules to explore space laterally, as they search for targets such as kinetochores.