Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany.
Nat Cell Biol. 2013 Jan;15(1):82-7. doi: 10.1038/ncb2640. Epub 2012 Dec 9.
During cell division, spindle microtubules attach to chromosomes through kinetochores, protein complexes on the chromosome. 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. The efficiency of search-and-capture can be improved by a bias in microtubule growth towards the kinetochores, by nucleation of microtubules at the kinetochores and at spindle microtubules, by kinetochore movement, or by a combination of these processes. 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.
在细胞分裂过程中,纺锤体微管通过着丝粒(染色体上的蛋白质复合物)附着在染色体上。核心问题是微管如何找到着丝粒。根据被称为搜索捕获的开创性观点,许多微管从中心体向各个方向生长,偶然捕获着丝粒。通过微管生长向着丝粒的偏差、着丝粒和纺锤体微管处微管的成核、着丝粒运动,或者这些过程的组合,可以提高搜索捕获的效率。在这里,我们在裂殖酵母中表明,微管通过围绕纺锤体极旋转来捕获着丝粒,而不是向着丝粒生长。微管的这种旋转运动是随机的,与 ATP 驱动的马达活动无关。通过引入一个理论模型,我们表明,测量到的微管和着丝粒的随机运动足以解释着丝粒捕获的过程。我们的理论预测捕获的速度主要取决于微管旋转的速度有多快,这通过加速和减缓微管旋转在实验中得到了证实。因此,旋转运动允许微管侧向探索空间,因为它们在寻找着丝粒等目标。