Tension promotes kinetochore-microtubule release by Aurora B kinase.
Tension promotes kinetochore-microtubule release by Aurora B kinase.
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DOI：
10.1083/jcb.202007030
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发表时间：
2021-06-07
期刊：
影响因子：
--
通讯作者：
Lampson MA
中科院分区：
文献类型：
--
作者：
Chen GY;Renda F;Zhang H;Gokden A;Wu DZ;Chenoweth DM;Khodjakov A;Lampson MA
Chen等人展示运动中枢如何利用Aurora B激酶的光基因操作来整合力学和生物化学。Aurora B在低张力下促进微管解聚或在高张力下促进微管释放。因此，紧张是一种信号，会导致不同的纠错路径。为了确保准确的染色体分离，动点和微管之间的相互作用由力学和生物化学相结合来调节。张力提供了一个信号，用来区分连接错误和双向着丝点，姐妹正确地连接到相反的纺锤杆上。在生物化学方面，Aurora B激酶使运动中枢磷酸化，从而破坏与微管的相互作用。为了将力学和生物化学联系起来，目前的模型将张力视为局部调节极光B活动的输入信号。在这里，我们证明了动粒磷酸化的结果取决于张力。利用光遗传学在个体运动中枢操纵Aurora B，我们发现当张力较高时，激酶活性促进微管释放。相反，当张力较低时，Aurora B的活性促进动粒微管的解聚，同时保持附着。因此，磷酸化将张力稳定附着体的捕获键转换为滑动键，在张力下释放微管。我们认为张力是诱导不同纠错途径的信号，释放或解聚分别有利于以高张力或低张力为特征的典型错误。
Chen et al. show how kinetochores integrate mechanics and biochemistry using optogenetic manipulation of Aurora B kinase. Aurora B promotes microtubule depolymerization at low tension or microtubule release at high tension. Thus, tension is a signal inducing distinct error-correction pathways. To ensure accurate chromosome segregation, interactions between kinetochores and microtubules are regulated by a combination of mechanics and biochemistry. Tension provides a signal to discriminate attachment errors from bi-oriented kinetochores with sisters correctly attached to opposite spindle poles. Biochemically, Aurora B kinase phosphorylates kinetochores to destabilize interactions with microtubules. To link mechanics and biochemistry, current models regard tension as an input signal to locally regulate Aurora B activity. Here, we show that the outcome of kinetochore phosphorylation depends on tension. Using optogenetics to manipulate Aurora B at individual kinetochores, we find that kinase activity promotes microtubule release when tension is high. Conversely, when tension is low, Aurora B activity promotes depolymerization of kinetochore–microtubules while maintaining attachment. Thus, phosphorylation converts a catch-bond, in which tension stabilizes attachments, to a slip-bond, which releases microtubules under tension. We propose that tension is a signal inducing distinct error-correction pathways, with release or depolymerization being advantageous for typical errors characterized by high or low tension, respectively.
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21.3
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