The human kinesin Kif18A is a motile microtubule depolymerase essential for chromosome congression
The human kinesin Kif18A is a motile microtubule depolymerase essential for chromosome congression
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DOI：
10.1016/j.cub.2007.02.036
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发表时间：
2007-03-20
期刊：
影响因子：
9.2
通讯作者：
Mayer, Thomas U.
中科院分区：
文献类型：
--
作者：
Mayr, Monika I.;Huemmer, Stefan;Mayer, Thomas U.
背景资料：染色体在纺锤体赤道的精确排列是有丝分裂中基因组平均分布的基础，因此也是真核生物遗传完整性的基础。虽然它是公认的，染色体运动耦合到微管动力学，基本的机制还没有很好地understood.Results：通过结合RNAi耗竭实验与体外生化测定，我们证明，人类驱动蛋白Kif 18 A是一个能动的微管解聚酶在哺乳动物组织培养细胞中的染色体congression必不可少的。我们发现，在体外Kif 18 A是一个缓慢的加端定向驱动蛋白，具有微管解聚活性。值得注意的是，Kif 18 A像它的酵母直系同源物Kip 3 p一样，解聚较长的微管比短的微管更快。在体内，Kif 18 A在有丝分裂中积累，在那里它定位于接近动粒微管的正端。Kif 18 A的缺失诱导异常长的有丝分裂纺锤体和跨姐妹动粒的张力损失，导致Mad 2依赖的纺锤体组装检查点的激活。活细胞显微镜的研究表明，在Kif 18 A-耗尽的细胞，染色体移动速度降低，完全无法在纺锤体equator.Conclusions对齐：这些研究确定Kif 18 A作为一个双重功能的驱动蛋白和哺乳动物细胞中染色体congression的关键组成部分。
Background: The accurate alignment of chromosomes at the spindle equator is fundamental for the equal distribution of the genome in mitosis and thus for the genetic integrity of eukaryotes. Although it is well established that chromosome movements are coupled to microtubule dynamics, the underlying mechanism is not well understood.Results: By combining RNAi-depletion experiments with in vitro biochemical assays, we demonstrate that the human kinesin Kif18A is a motile microtubule depolymerase essential for chromosome congression in mammalian tissue culture cells. We show that in vitro Kif18A is a slow plus-end-directed kinesin that possesses microtubule depolymerizing activity. Notably, Kif18A like its yeast ortholog Kip3p depolymerizes longer microtubules more quickly than shorter ones. In vivo, Kif18A accumulates in mitosis where it localizes close to the plus ends of kinetochore microtubules. The depletion of Kif18A induces aberrantly long mitotic spindles and loss of tension across sister kinetochores, resulting in the activation of the Mad2-dependent spindie-assembly checkpoint. Live-cell microscopy studies revealed that in Kif18A-depleted cells, chromosomes move at reduced speed and completely fail to align at the spindle equator.Conclusions: These studies identify Kif18A as a dual-functional kinesin and a key component of chromosome congression in mammalian cells.