研究动态
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小鼠卵母细胞中极光蛋白激酶的遗传相互作用作图。

Genetic interaction mapping of Aurora protein kinases in mouse oocytes.

发表日期:2024
作者: Cecilia S Blengini, Karen Schindler
来源: Frontiers in Cell and Developmental Biology

摘要:

极光激酶 (AURK) 是对细胞分裂至关重要的丝氨酸-苏氨酸蛋白激酶家族。体细胞仅表达 AURKA 和 AURKB。然而,哺乳动物生殖细胞和一些癌细胞表达所有三种亚型。该领域的一个主要问题是确定当细胞表达三种而不是两种极光激酶时分子和细胞的变化。使用涉及不同极光激酶卵母细胞特异性敲除组合的系统遗传方法,我们完成了卵母细胞-AURK遗传相互作用图谱,并表明Aurka的一个基因组拷贝对于支持女性生育力和卵母细胞减数分裂是必要且充分的。我们进一步确认,仅靠 AURKB 和 AURKC 无法弥补 AURKA。这些结果强调了 AURKA 在小鼠卵母细胞中的重要性,证明它是纺锤体形成和正确染色体分离所必需的。令人惊讶的是,一部分缺乏 AURKB 的卵母细胞可以完成减数分裂 I,但这些卵子的质量受到损害,这表明 AURKB 具有调节纺锤体组装检查点或控制细胞周期的作用。结合我们之前的研究,我们全面定义了 Aurora 激酶之间的遗传相互作用,并强调了 AURKA 表达在卵母细胞减数分裂中的重要性。版权所有 © 2024 Blenginini 和 Schindler。
The Aurora Kinases (AURKs) are a family of serine-threonine protein kinases critical for cell division. Somatic cells express only AURKA and AURKB. However, mammalian germ cells and some cancer cells express all three isoforms. A major question in the field has been determining the molecular and cellular changes when cells express three instead of two aurora kinases. Using a systematic genetic approach involving different Aurora kinase oocyte-specific knockout combinations, we completed an oocyte-AURK genetic interaction map and show that one genomic copy of Aurka is necessary and sufficient to support female fertility and oocyte meiosis. We further confirm that AURKB and AURKC alone cannot compensate for AURKA. These results highlight the importance of AURKA in mouse oocytes, demonstrating that it is required for spindle formation and proper chromosome segregation. Surprisingly, a percentage of oocytes that lack AURKB can complete meiosis I, but the quality of those eggs is compromised, suggesting a role in AURKB to regulate spindle assembly checkpoint or control the cell cycle. Together with our previous studies, we wholly define the genetic interplay among the Aurora kinases and reinforce the importance of AURKA expression in oocyte meiosis.Copyright © 2024 Blengini and Schindler.