A TOG Protein Confers Tension Sensitivity to Kinetochore-Microtubule Attachments.
A TOG Protein Confers Tension Sensitivity to Kinetochore-Microtubule Attachments.
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DOI：
10.1016/j.cell.2016.04.030
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发表时间：
2016-06-02
期刊：
影响因子：
64.5
通讯作者：
Biggins S
中科院分区：
文献类型：
--
作者：
Miller MP;Asbury CL;Biggins S
所有生物的发育和生存都依赖于细胞分裂过程中基因组的均匀分割。准确的染色体分离需要有选择性地稳定着丝点与微管的连接，这些连接由于动态微管尖端施加在姐妹着丝点上的相反拉力而受到张力。在这里，我们发现XMAP215家族成员Stu2对着丝点-微管偶联做出了重要贡献。Stu2及其人类同源物ch-TOG与Ndc80着丝点复合物表现出保守的相互作用，加强了其与微管尖端的附着。引人注目的是，Stu2可以稳定或破坏着丝点的附着，这取决于着丝点的张力水平和微管尖端是组装还是拆卸。Stu2的这些二元效应独立于其先前研究的微管动力学调节。总之，我们的研究结果证明了着丝酶相关因子如何赋予相反的张力依赖效应，以选择性地稳定张力承载附件，为染色体分离过程中准确性的基础提供了机制见解。
The development and survival of all organisms depends on equal partitioning of their genomes during cell division. Accurate chromosome segregation requires selective stabilization of kinetochore-microtubule attachments that come under tension due to opposing pulling forces exerted on sister kinetochores by dynamic microtubule tips. Here, we show that the XMAP215 family member, Stu2, makes a major contribution to kinetochore-microtubule coupling. Stu2 and its human ortholog, ch-TOG, exhibit a conserved interaction with the Ndc80 kinetochore complex that strengthens its attachment to microtubule tips. Strikingly, Stu2 can either stabilize or destabilize kinetochore attachments, depending on the level of kinetochore tension and whether the microtubule tip is assembling or disassembling. These dichotomous effects of Stu2 are independent of its previously studied regulation of microtubule dynamics. Altogether, our results demonstrate how a kinetochore-associated factor can confer opposing, tension-dependent effects to selectively stabilize tension-bearing attachments, providing mechanistic insight into the basis for accuracy during chromosome segregation.