Microtubule binding by KNL-1 contributes to spindle checkpoint silencing at the kinetochore.

Microtubule binding by KNL-1 contributes to spindle checkpoint silencing at the kinetochore.
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DOI:
10.1083/jcb.201111107
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发表时间:
2012-02-20
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Desai A
Desai A
中科院分区:
其他
文献类型:
--
作者:
Espeut J;Cheerambathur DK;Krenning L;Oegema K;Desai A

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一个微管结合位点在极端的N末端的KNL-1是固定的承重附件,但参与检查点沉默在动粒。准确的染色体分离需要微管附着和纺锤体检查点信号在动粒之间的协调。Kinetochore-localized KMN(KNL-1/Mis 12复合物/Ndc 80复合物)网络介导微管附着和支架检查点信号传导,具有两种不同的微管结合活性:Ndc 80复合物的承重活性和KNL-1中不太了解的活性。在本文中,我们表明,KNL-1微管结合和捆绑活动驻留在其极端的N末端。在秀丽隐杆线虫胚胎中选择性扰动KNL-1微管结合揭示了这种活性对于承重附着形成和检查点激活都是不稳定的,但在动粒的检查点沉默中起作用。微管结合和蛋白磷酸酶1在KNL-1 N末端的对接的扰动加性地影响检查点沉默,这表明,尽管它们在KNL-1中接近,但这两种活动做出独立的贡献。我们提出,微管结合KNL-1的功能,在检查点沉默的检测微管连接到动粒和中继它们的存在,以消除检查点信号的产生。
A microtubule-binding site in the extreme N terminus of KNL-1 is dispensable for load-bearing attachments but participates in checkpoint silencing at the kinetochore. Accurate chromosome segregation requires coordination between microtubule attachment and spindle checkpoint signaling at the kinetochore. The kinetochore-localized KMN (KNL-1/Mis12 complex/Ndc80 complex) network, which mediates microtubule attachment and scaffolds checkpoint signaling, harbors two distinct microtubule-binding activities: the load-bearing activity of the Ndc80 complex and a less well-understood activity in KNL-1. In this paper, we show that KNL-1 microtubule-binding and -bundling activity resides in its extreme N terminus. Selective perturbation of KNL-1 microtubule binding in Caenorhabditis elegans embryos revealed that this activity is dispensable for both load-bearing attachment formation and checkpoint activation but plays a role in checkpoint silencing at the kinetochore. Perturbation of both microtubule binding and protein phosphatase 1 docking at the KNL-1 N terminus additively affected checkpoint silencing, indicating that, despite their proximity in KNL-1, these two activities make independent contributions. We propose that microtubule binding by KNL-1 functions in checkpoint silencing by sensing microtubules attached to kinetochores and relaying their presence to eliminate generation of the checkpoint signal.
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