Microtubule cross-linking activity of She1 ensures spindle stability for spindle positioning.

Microtubule cross-linking activity of She1 ensures spindle stability for spindle positioning.
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DOI:
10.1083/jcb.201701094
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发表时间:
2017-09-04
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Lee WL
Lee WL
中科院分区:
其他
文献类型:
--
作者:
Zhu Y;An X;Tomaszewski A;Hepler PK;Lee WL

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动力蛋白通过从大脑皮层拉出星体微管来定位纺锤体。在酿酒酵母中,微管相关蛋白SHE1特异性地抑制母室中的动力蛋白,以促进纺锤体向芽中移动。朱等人。证明SHE1还稳定极间微管,确保在动力蛋白介导的纺锤体定位过程中纺锤体的完整性。动力蛋白通过拉动细胞皮质中的星形微管(MTS)来调节萌芽酵母中的纺锤体定位。MT相关蛋白She1调节沿星体MT的动力蛋白活动,并引导纺锤体向芽细胞移动。除了定位于星形MTS外,She1还定位于纺锤体,但其在纺锤体上的作用尚不清楚。利用功能分离等位基因、活细胞纺锤体分析和体外生化分析,我们证明She1是维持中期纺锤体稳定所必需的。SHE1通过C端MT结合位点与MT结合并使其发生交叉连接。SHE1也可以自组装成环状低聚物。在细胞中,She1稳定极间MTS,防止运动中的纺锤体变形,我们证明这一活性在细胞周期进展中受Ipl1/Aurora B磷酸化的调节。我们的数据揭示了在纺锤体穿过芽颈的运动过程中,She1如何确保纺锤体的完整性,并暗示了纺锤体完整性的调节和动力蛋白途径活动之间的潜在联系。
Dynein orients the spindle by pulling on astral microtubules from the cortex. In Saccharomyces cerevisiae, the microtubule-associated protein She1 specifically inhibits dynein in the mother compartment to promote spindle movements toward the bud. Zhu et al. demonstrate that She1 also stabilizes interpolar microtubules, ensuring spindle integrity during dynein-mediated spindle positioning. Dynein mediates spindle positioning in budding yeast by pulling on astral microtubules (MTs) from the cell cortex. The MT-associated protein She1 regulates dynein activity along astral MTs and directs spindle movements toward the bud cell. In addition to localizing to astral MTs, She1 also targets to the spindle, but its role on the spindle remains unknown. Using function-separating alleles, live-cell spindle assays, and in vitro biochemical analyses, we show that She1 is required for the maintenance of metaphase spindle stability. She1 binds and cross-links MTs via a C-terminal MT-binding site. She1 can also self-assemble into ring-shaped oligomers. In cells, She1 stabilizes interpolar MTs, preventing spindle deformations during movement, and we show that this activity is regulated by Ipl1/Aurora B phosphorylation during cell cycle progression. Our data reveal how She1 ensures spindle integrity during spindle movement across the bud neck and suggest a potential link between regulation of spindle integrity and dynein pathway activity.
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