A functional analysis of MELK in cell division reveals a transition in the mode of cytokinesis during Xenopus development

A functional analysis of MELK in cell division reveals a transition in the mode of cytokinesis during Xenopus development
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DOI:
10.1242/jcs.069567
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发表时间:
2011-03-15
影响因子:
4
通讯作者:
Tassan, Jean-Pierre
Tassan, Jean-Pierre
中科院分区:
生物学2区
文献类型:
--
作者:
Le Page, Yann;Chartrain, Isabelle;Tassan, Jean-Pierre

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MELK是一种丝氨酸/苏氨酸激酶,参与多种细胞过程,包括细胞周期、增殖、凋亡和mRNA加工。然而,其功能仍然难以捉摸。在这里,我们探索了它在非洲爪蟾早期胚胎中的作用,并通过敲除表明xMELK(非洲爪蟾MELK)对于完成细胞分裂是必需的。与细胞分裂中的作用一致,内源性xMELK在后期卵裂球的赤道皮质处积累。它的重新定位是高度动态的,并与xMELK中的构象重排相关。xMELK的过表达导致胞质分裂失败,并损害激活的RhoA(胞质分裂的关键调节因子)在分裂沟处的积累。此外,内源性xMELK与胞质分裂组织者苯胺结合并共定位。出乎意料的是,我们的研究揭示了与细胞大小相关的胞质分裂模式的转变,这涉及xMELK。总的来说,我们的研究结果揭示了xMELK在早期发育过程中胞质分裂的重要性,并表明胞质分裂的机制在非洲爪蟾早期发育过程中发生了变化。
MELK is a serine/threonine kinase involved in several cell processes, including the cell cycle, proliferation, apoptosis and mRNA processing. However, its function remains elusive. Here, we explored its role in the Xenopus early embryo and show by knockdown that xMELK (Xenopus MELK) is necessary for completion of cell division. Consistent with a role in cell division, endogenous xMELK accumulates at the equatorial cortex of anaphase blastomeres. Its relocalization is highly dynamic and correlates with a conformational rearrangement in xMELK. Overexpression of xMELK leads to failure of cytokinesis and impairs accumulation at the division furrow of activated RhoA - a pivotal regulator of cytokinesis. Furthermore, endogenous xMELK associates and colocalizes with the cytokinesis organizer anillin. Unexpectedly, our study reveals a transition in the mode of cytokinesis correlated to cell size and that implicates xMELK. Collectively, our findings disclose the importance of xMELK in cytokinesis during early development and show that the mechanism of cytokinesis changes during Xenopus early development.