The human kinetochore Ska1 complex facilitates microtubule depolymerization-coupled motility.

The human kinetochore Ska1 complex facilitates microtubule depolymerization-coupled motility.
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DOI:
10.1016/j.devcel.2009.01.011
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发表时间:
2009-03
期刊:
影响因子:
11.8
通讯作者:
Cheeseman, Iain M.
Cheeseman, Iain M.
中科院分区:
生物学1区
文献类型:
--
作者:
Welburn, Julie P. I.;Grishchuk, Ekaterina L.;Backer, Chelsea B.;Wilson-Kubalek, Elizabeth M.;Yates, John R., III;Cheeseman, Iain M.

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有丝分裂染色体分离需要动点附着在微管聚合物上,并利用微管动力学来驱动染色体运动。在萌芽酵母中,DAM1复合体将动点与微管解聚结合在一起。然而,尚未确定DAM1复合体的后生动物同源物。为了确定在脊椎动物动粒中心-微管界面上发挥相应作用的蛋白质,我们分离了一个3亚单位的人类Ska1复合体,包括先前未鉴定的蛋白Rama1,它定位于外部动粒中心和纺锤体微管。Ska1复合体亚基的缺失严重影响了染色体的正常分离。重组的Ska1复合体具有两种可分离的生化活性:通过Ska1亚基直接与微管结合和通过Rama1亚基实现微管刺激的寡聚作用。完整的Ska1复合体在微管上形成组装,可以促进微球沿着解聚的微管进行移动。总之,这些结果证明了Ska1复合体在与外部动粒上的动态微管相互作用中发挥着关键作用。
Mitotic chromosome segregation requires that kinetochores attach to microtubule polymers and harness microtubule dynamics to drive chromosome movement. In budding yeast, the Dam1 complex couples kinetochores with microtubule depolymerization. However, a metazoan homologue of the Dam1 complex has not been identified. To identify proteins that play a corresponding role at the vertebrate kinetochore-microtubule interface, we isolated a 3-subunit human Ska1 complex, including the previously uncharacterized protein Rama1, that localizes to the outer kinetochore and spindle microtubules. Depletion of Ska1 complex subunits severely compromises proper chromosome segregation. Reconstituted Ska1 complex possesses two separable biochemical activities; direct microtubule-binding through the Ska1 subunit, and microtubule-stimulated oligomerization imparted by the Rama1 subunit. The full Ska1 complex forms assemblies on microtubules that can facilitate the processive movement of microspheres along depolymerizing microtubules. In total, these results demonstrate a critical role for the Ska1 complex in interacting with dynamic microtubules at the outer kinetochore.
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