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极光 B 控制着锥体虫的后期起始和无差错的染色体分离。

Aurora B controls anaphase onset and error-free chromosome segregation in trypanosomes.

机构信息

Department of Biochemistry, University of Oxford, Oxford, UK.

The Wellcome Centre for Cell Biology, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, UK.

出版信息

J Cell Biol. 2024 Nov 4;223(11). doi: 10.1083/jcb.202401169. Epub 2024 Aug 28.

Abstract

Kinetochores form the interface between chromosomes and spindle microtubules and are thus under tight control by a complex regulatory circuitry. The Aurora B kinase plays a central role within this circuitry by destabilizing improper kinetochore-microtubule attachments and relaying the attachment status to the spindle assembly checkpoint. Intriguingly, Aurora B is conserved even in kinetoplastids, a group of early-branching eukaryotes which possess a unique set of kinetochore proteins. It remains unclear how their kinetochores are regulated to ensure faithful chromosome segregation. Here, we show in Trypanosoma brucei that Aurora B activity controls the metaphase-to-anaphase transition through phosphorylation of the divergent Bub1-like protein KKT14. Depletion of KKT14 overrides the metaphase arrest resulting from Aurora B inhibition, while expression of non-phosphorylatable KKT14 delays anaphase onset. Finally, we demonstrate that re-targeting Aurora B to the outer kinetochore suffices to promote mitotic exit but causes extensive chromosome missegregation in anaphase. Our results indicate that Aurora B and KKT14 are involved in an unconventional circuitry controlling cell cycle progression in trypanosomes.

摘要

动粒作为染色体与纺锤体微管的连接界面,受到一个复杂的调控网络的严格控制。Aurora B 激酶在这个调控网络中起着核心作用,它通过破坏不正确的动粒-微管连接,并将连接状态传递给纺锤体组装检查点,从而发挥作用。有趣的是,Aurora B 在动基体生物中也被保守,动基体生物是一组早期分支的真核生物,它们拥有一套独特的动粒蛋白。目前尚不清楚它们的动粒是如何被调控以确保染色体的正确分离。在这里,我们在布氏锥虫中表明,Aurora B 的活性通过磷酸化差异表达的 Bub1 样蛋白 KKT14 来控制从中期到后期的转变。KKT14 的缺失会忽略由于 Aurora B 抑制而导致的中期停滞,而表达不可磷酸化的 KKT14 则会延迟后期的开始。最后,我们证明将 Aurora B 重新靶向到外动粒足以促进有丝分裂退出,但在后期会导致广泛的染色体错误分离。我们的研究结果表明,Aurora B 和 KKT14 参与了一个控制锥虫细胞周期进程的非常规调控网络。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/53a9/11354203/4112c8b8b730/JCB_202401169_FigS1.jpg

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