Ipl1/Aurora-dependent phosphorylation of Sli15/INCENP regulates CPC-spindle interaction to ensure proper microtubule dynamics.

Ipl1/Aurora-dependent phosphorylation of Sli15/INCENP regulates CPC-spindle interaction to ensure proper microtubule dynamics.
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DOI:
10.1083/jcb.201009137
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发表时间:
2011-07-11
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Barnes G
Barnes G
中科院分区:
其他
文献类型:
--
作者:
Nakajima Y;Cormier A;Tyers RG;Pigula A;Peng Y;Drubin DG;Barnes G

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Ipl1/Aurora 介导的 CPC 成分 Sli15/INCENP 磷酸化通过限制 CPC-纺锤体关联来促进微管动力学。动态微管有利于后期之前的染色体排列,而在后期微管稳定性有助于染色体分离。中期-后期转变时微管动力学的变化受 Cdk1 调节。 Cdk1 介导的 Sli15/INCENP 磷酸化通过阻止染色体过客复合物(CPC;Sli15/INCENP、Bir1/Survivin、Nbl1/Borealin、Ipl1/Aurora)与纺锤体的关联来促进后期微管动力学。然而,Cdk1 是否单独控制微管动力学,以及 CPC-微管关联如何影响微管行为,尚不清楚。在这里,我们发现 Sli15/INCENP 的 Ipl1/Aurora 依赖性磷酸化通过阻止 CPC 与前期纺锤体和中央纺锤体结合直到后期后期来调节微管动力学,从而促进正确中期着丝粒定位和后期纺锤体伸长所需的微管动力学的时空控制。 Ipl1 依赖性 Sli15 磷酸化的减少驱动 CPC 与微管的直接结合,揭示了 CPC 如何影响微管动力学。我们提出,Cdk1 和 Ipl1/Aurora 协同调节微管动力学,并且 Ipl1/Aurora 依赖性的 Sli15 磷酸化通过将 CPC 排除在参与微管聚合的纺锤体区域来控制纺锤体功能。
Ipl1/Aurora-mediated phosphorylation of the CPC component Sli15/INCENP promotes microtubule dynamics by restricting CPC–spindle association. Dynamic microtubules facilitate chromosome arrangement before anaphase, whereas during anaphase microtubule stability assists chromosome separation. Changes in microtubule dynamics at the metaphase–anaphase transition are regulated by Cdk1. Cdk1-mediated phosphorylation of Sli15/INCENP promotes preanaphase microtubule dynamics by preventing chromosomal passenger complex (CPC; Sli15/INCENP, Bir1/Survivin, Nbl1/Borealin, Ipl1/Aurora) association with spindles. However, whether Cdk1 has sole control over microtubule dynamics, and how CPC–microtubule association influences microtubule behavior, are unclear. Here, we show that Ipl1/Aurora-dependent phosphorylation of Sli15/INCENP modulates microtubule dynamics by preventing CPC binding to the preanaphase spindle and to the central spindle until late anaphase, facilitating spatiotemporal control of microtubule dynamics required for proper metaphase centromere positioning and anaphase spindle elongation. Decreased Ipl1-dependent Sli15 phosphorylation drives direct CPC binding to microtubules, revealing how the CPC influences microtubule dynamics. We propose that Cdk1 and Ipl1/Aurora cooperatively modulate microtubule dynamics and that Ipl1/Aurora-dependent phosphorylation of Sli15 controls spindle function by excluding the CPC from spindle regions engaged in microtubule polymerization.
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