The kinesin-8 Kip3 scales anaphase spindle length by suppression of midzone microtubule polymerization.
The kinesin-8 Kip3 scales anaphase spindle length by suppression of midzone microtubule polymerization.
复制标题
DOI：
10.1083/jcb.201312039
复制
发表时间：
2014-03-17
期刊：
影响因子：
--
通讯作者：
Gupta ML Jr
中科院分区：
文献类型：
--
作者：
Rizk RS;Discipio KA;Proudfoot KG;Gupta ML Jr
Kip 3的解聚酶活性抑制纺锤体微管聚合以限制纺锤体中间区长度并防止微管响应于滑动力而屈曲。有丝分裂纺锤体功能对于细胞分裂和基因组稳定性至关重要。在分裂后期，伸长的纺锤体物理分离姐妹染色单体。然而，决定后期纺锤体伸长程度的分子机制仍不清楚。在筛选纺锤体长度改变的酵母突变体中，我们确定了驱动蛋白-8 Kip 3对细胞大小缩放纺锤体长度至关重要。Kip 3是一种多功能的运动蛋白，具有微管解聚酶、正末端运动和反平行滑动活性。在这里，我们表明，解聚酶的活动是必不可少的控制纺锤体的长度，而运动和滑动活动是不够的。此外，微管去稳定化活性需要抵消Stu 2/XMAP 215介导的微管聚合，使得一旦纺锤体达到适当的最终长度，纺锤体伸长终止。我们的数据支持Kip 3直接抑制纺锤体微管聚合，限制中间区长度的模型。因此，中间区内的滑动力不能使纺锤体微管弯曲，这允许细胞边界限定纺锤体伸长的程度。
The depolymerase activity of Kip3 suppresses spindle microtubule polymerization to limit spindle midzone length and prevent microtubule buckling in response to sliding forces. Mitotic spindle function is critical for cell division and genomic stability. During anaphase, the elongating spindle physically segregates the sister chromatids. However, the molecular mechanisms that determine the extent of anaphase spindle elongation remain largely unclear. In a screen of yeast mutants with altered spindle length, we identified the kinesin-8 Kip3 as essential to scale spindle length with cell size. Kip3 is a multifunctional motor protein with microtubule depolymerase, plus-end motility, and antiparallel sliding activities. Here we demonstrate that the depolymerase activity is indispensable to control spindle length, whereas the motility and sliding activities are not sufficient. Furthermore, the microtubule-destabilizing activity is required to counteract Stu2/XMAP215-mediated microtubule polymerization so that spindle elongation terminates once spindles reach the appropriate final length. Our data support a model where Kip3 directly suppresses spindle microtubule polymerization, limiting midzone length. As a result, sliding forces within the midzone cannot buckle spindle microtubules, which allows the cell boundary to define the extent of spindle elongation.