SKAP interacts with Aurora B to guide end-on capture of spindle microtubules via phase separation.

SKAP interacts with Aurora B to guide end-on capture of spindle microtubules via phase separation.
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SKAP 与 Aurora B 相互作用,通过相分离引导纺锤体微管的末端捕获

DOI:
10.1093/jmcb/mjab058
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发表时间:
2022-01-29
影响因子:
5.5
通讯作者:
Yao X
Yao X
中科院分区:
生物学1区
文献类型:
--
作者:
Zhang M;Yang F;Wang W;Zohbi N;Wang X;Wang D;Zhuang X;Dou Z;Liu D;Song X;Green HN;Liu X;Yao X

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有丝分裂中的染色体分离是由着丝粒和纺锤体微管之间的动态相互作用所调控的。我们最近的研究表明,有丝分裂马达CENP-E与Skap协同作用,在动粒核心MIS13复合体和纺锤体微管加端之间形成联系,实现有丝分裂中染色体的精确配对。然而,在中期对齐过程中,Skap如何调节着丝粒从侧向连接到末端连接仍然是个未知数。在这里,我们发现了Aurora B和Skap之间的一种新的相互作用,它协调着动粒和动态纺锤体微管之间的准确相互作用。有趣的是,Skap在体外通过弱的多价相互作用自发地相分离成具有快速内部动力学的液滴。Skap和Aurora B在体外形成异质凝聚体,概括了Skap彗星在体内的动力学和行为。重要的是,Skap与Aurora B通过相分离的相互作用对于准确的染色体分离和比对是必不可少的。基于这些发现,我们推测,在动粒-微管连接的侧向到端的转化过程中,通过相分离的Skap-Aurora B相互作用构成了Aurora B活动的动态池,以实现细胞的忠实分裂。
Chromosome segregation in mitosis is orchestrated by the dynamic interactions between the kinetochore and spindle microtubules. Our recent studies show that mitotic motor CENP-E cooperates with SKAP and forms a link between kinetochore core MIS13 complex and spindle microtubule plus-ends to achieve accurate chromosome alignment in mitosis. However, it remains elusive how SKAP regulates kinetochore attachment from lateral association to end-on attachment during metaphase alignment. Here, we identify a novel interaction between Aurora B and SKAP that orchestrates accurate interaction between the kinetochore and dynamic spindle microtubules. Interestingly, SKAP spontaneously phase-separates in vitro via weak, multivalent interactions into droplets with fast internal dynamics. SKAP and Aurora B form heterogeneous coacervates in vitro, which recapitulate the dynamics and behavior of SKAP comets in vivo. Importantly, SKAP interaction with Aurora B via phase separation is essential for accurate chromosome segregation and alignment. Based on those findings, we reason that SKAP–Aurora B interaction via phase separation constitutes a dynamic pool of Aurora B activity during the lateral to end-on conversion of kinetochore–microtubule attachments to achieve faithful cell division.
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