运动蛋白样蛋白KIF18A是染色体组装与细胞分裂的忠实协调所必需的。

Su Hyun Lee, Mi-Sun Kwon, Taerim Lee, Sungchul Hohng, Hyunsook Lee
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引用次数: 0

摘要

维持增殖细胞的遗传完整性需要DNA复制、染色体分离和细胞动力学脱落的协调调节。染色体-微管相互作用调节有丝分裂,而肌动蛋白骨架和肌球蛋白IIA之间的相互作用决定细胞动力学脱落。这一过程对复制基因组在两个子细胞中的均匀分布至关重要,它垂直于染色体分离轴。然而,微管驱动的有丝分裂和肌动蛋白相关的细胞分裂如何精确协调的机制仍然知之甚少。本研究强调了KIF18A(一种类似于动蛋白的蛋白)在连接着丝点-微管动力学与细胞动力学轴形成中的作用。KIF18A的定位在整个细胞分裂周期中发生变化,从染色体大会中期的板到后期的中央纺锤体,最后到末期的纺锤体中部。KIF18A缺失导致染色体组装失败和后期开始延迟。值得注意的是,在没有KIF18A的情况下,试图进行分裂的细胞表现出中央纺锤体平行结构的破坏,导致中央纺锤体复合体的错误定位,例如运动蛋白样蛋白KIF23(也称为MKLP1)和Rac gtpase激活蛋白1 (RACGAP1)。这些破坏破坏了分裂沟的建立,导致细胞分裂不完全和单核或双核细胞的形成。我们的研究结果表明,KIF18A通过调节后期中央纺锤体的空间和时间组装,在协调染色体聚集和细胞分裂中起着至关重要的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Kinesin-like protein KIF18A is required for faithful coordination of chromosome congression with cytokinesis.

The maintenance of genetic integrity in proliferating cells requires the coordinated regulation of DNA replication, chromosome segregation, and cytokinetic abscission. Chromosome-microtubule interactions regulate mitosis, while interactions between the actin cytoskeleton and Myosin IIA dictate cytokinetic abscission. This process, crucial for the equal distribution of the duplicated genome into two daughter cells, occurs perpendicular to the axis of chromosome segregation. However, the mechanism of how microtubule-driven mitosis and actin-associated cytokinesis are precisely coordinated remains poorly understood. This study highlights the role of KIF18A, a kinesin-like protein, in linking kinetochore-microtubule dynamics to cytokinetic axis formation. KIF18A's localization changes through the cell division cycle, from the metaphase plate during chromosome congression to the central spindle in late anaphase, and finally to the spindle midbody in telophase. KIF18A depletion leads to chromosome congression failures and anaphase onset delays. Notably, cells attempting to undergo division in the absence of KIF18A exhibited disruptions in the parallel structure of the central spindle, causing mislocalization of the centralspindlin complex, such as kinesin-like protein KIF23 (also known as MKLP1) and Rac GTPase-activating protein 1 (RACGAP1). These disruptions impair cleavage furrow establishment, causing incomplete cytokinesis and the formation of mononuclear or binucleated cells. Our findings suggest that KIF18A is crucial for coordinating chromosome congression and cytokinesis by regulating the spatial and temporal assembly of the central spindle during late anaphase.

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