Cell Cycle and Cancer Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
J Cell Sci. 2022 Feb 1;135(3). doi: 10.1242/jcs.258745. Epub 2022 Feb 2.
The microtubules of the mitotic spindle mediate chromosome alignment to the metaphase plate, then sister chromatid segregation to the spindle poles in anaphase. Previous analyses of spindle microtubule kinetics utilizing fluorescence dissipation after photoactivation described two main populations, a slow and a fast turnover population, and these were ascribed as reflecting kinetochore versus non-kinetochore microtubules, respectively. Here, we test this categorization by disrupting kinetochores through depletion of the Ndc80 complex in U2OS cells. In the absence of functional kinetochores, microtubule dynamics still exhibit slow and fast turnover populations, although the proportion of each population and the timings of turnover are altered. Importantly, the data obtained following Hec1 (also known as Ndc80) depletion suggests that other subpopulations, in addition to kinetochore microtubules, contribute to the slow turnover population. Further manipulation of spindle microtubules revealed a complex landscape. For example, although Aurora B kinase functions to destabilize kinetochore bound microtubules it might also stabilize certain slow turnover non-kinetochore microtubules. Dissection of the dynamics of microtubule populations provides a greater understanding of mitotic spindle kinetics and insight into their roles in facilitating chromosome attachment, movement and segregation during mitosis.
有丝分裂纺锤体的微管介导染色体排列到中期板上,然后在后期将姐妹染色单体分离到纺锤体极。以前利用光激活后的荧光耗散分析纺锤体微管动力学的分析描述了两个主要群体,一个是缓慢的和一个快速的周转率群体,分别归因于分别反映动粒微管和非动粒微管。在这里,我们通过耗尽 U2OS 细胞中的 Ndc80 复合物来破坏动粒,从而测试这种分类。在没有功能动粒的情况下,微管动力学仍然表现出缓慢和快速的周转率群体,尽管每个群体的比例和周转率的时间都发生了变化。重要的是,在 Hec1(也称为 Ndc80)耗竭后获得的数据表明,除了动粒微管之外,其他亚群也有助于缓慢周转率群体。进一步操纵纺锤体微管揭示了一个复杂的景观。例如,尽管 Aurora B 激酶的功能是使动粒结合的微管不稳定,但它也可能稳定某些缓慢周转率的非动粒微管。微管群体动力学的剖析提供了对有丝分裂纺锤体动力学的更深入理解,并深入了解它们在促进有丝分裂过程中染色体附着、运动和分离中的作用。