Daniel Ballmer, Hua Jane Lou, Midori Ishii, Benjamin E Turk, Bungo Akiyoshi
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引用次数: 0
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.
动点形成染色体与纺锤体微管之间的界面,因此受到复杂的调控电路的严格控制。极光 B 激酶在这一电路中起着核心作用,它能破坏不正常的动点核心-微管连接的稳定性,并将连接状态传递给纺锤体组装检查点。耐人寻味的是,极光 B 甚至在真核细胞中也是保守的,真核细胞是一类早期分支真核生物,拥有一套独特的动点核心蛋白。目前仍不清楚它们的动点如何调控以确保染色体的忠实分离。在这里,我们在布氏锥虫中发现,极光 B 的活性通过磷酸化不同的 Bub1 样蛋白 KKT14 来控制着色期到无色期的转变。KKT14的耗竭会推翻极光B抑制导致的无丝分裂期停滞,而不可磷酸化的KKT14的表达会延迟无丝分裂期的开始。最后,我们证明将 Aurora B 重新定向到外侧动点足以促进有丝分裂的退出,但在无丝分裂期会导致广泛的染色体错聚。我们的研究结果表明,极光 B 和 KKT14 参与了控制锥虫细胞周期进展的非常规电路。
期刊介绍:
The Journal of Cell Biology (JCB) is a comprehensive journal dedicated to publishing original discoveries across all realms of cell biology. We invite papers presenting novel cellular or molecular advancements in various domains of basic cell biology, along with applied cell biology research in diverse systems such as immunology, neurobiology, metabolism, virology, developmental biology, and plant biology. We enthusiastically welcome submissions showcasing significant findings of interest to cell biologists, irrespective of the experimental approach.