AURKA controls oocyte spindle assembly checkpoint and chromosome alignment by HEC1 phosphorylation.

IF 2.9 2区 生物学 Q1 BIOLOGY
Life Science Alliance Pub Date : 2025-05-06 Print Date: 2025-07-01 DOI:10.26508/lsa.202403146
Cecilia S Blengini, Shuang Tang, Robert J Mendola, G John Garrisi, Jason E Swain, Karen Schindler
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引用次数: 0

Abstract

In human oocytes, meiosis I is error-prone, causing early miscarriages and developmental disorders. The Aurora protein kinases are key regulators of chromosome segregation in mitosis and meiosis, and their dysfunction is associated with aneuploidy. Oocytes express three Aurora kinase (AURK) proteins, but only AURKA is necessary and sufficient to support oocyte meiosis in mice. However, the unique molecular contributions to ensuring high egg quality of AURKA remain unclear. Here, using a combination of genetic and pharmacological approaches, we evaluated how AURKA phosphorylation regulates outer kinetochore function during oocyte meiosis. We found that the outer kinetochore protein Ndc80/HEC1 is constitutively phosphorylated at multiple residues by Aurora kinases during meiosis I, but that serine 69 is specifically phosphorylated by AURKA in mouse and human oocytes. We further show that serine 69 phosphorylation contributes to spindle assembly checkpoint activation and chromosome alignment during meiosis I. These results provide a fundamental mechanistic understanding of how AURKA regulates meiosis and kinetochore function to ensure meiosis I fidelity.

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AURKA通过HEC1磷酸化控制卵母细胞纺锤体组装检查点和染色体排列。
在人类卵母细胞中,减数分裂I是容易出错的,导致早期流产和发育障碍。Aurora蛋白激酶是有丝分裂和减数分裂中染色体分离的关键调节因子,其功能障碍与非整倍体有关。卵母细胞表达三种极光激酶(AURK)蛋白,但只有AURKA是支持小鼠卵母细胞减数分裂所必需和充分的。然而,确保AURKA高卵子质量的独特分子作用仍不清楚。在这里,我们使用遗传和药理学方法的结合,我们评估了AURKA磷酸化如何调节卵母细胞减数分裂过程中的外着丝点功能。我们发现,在减数分裂I期间,外着丝点蛋白Ndc80/HEC1在多个残基上被Aurora激酶组成性磷酸化,但丝氨酸69在小鼠和人卵母细胞中被AURKA特异性磷酸化。我们进一步表明,丝氨酸69磷酸化有助于减数分裂I期间纺锤体组装检查点激活和染色体对齐。这些结果为AURKA如何调节减数分裂和着丝点功能以确保减数分裂I保真度提供了基本的机制理解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Life Science Alliance
Life Science Alliance Agricultural and Biological Sciences-Plant Science
CiteScore
5.80
自引率
2.30%
发文量
241
审稿时长
10 weeks
期刊介绍: Life Science Alliance is a global, open-access, editorially independent, and peer-reviewed journal launched by an alliance of EMBO Press, Rockefeller University Press, and Cold Spring Harbor Laboratory Press. Life Science Alliance is committed to rapid, fair, and transparent publication of valuable research from across all areas in the life sciences.
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