小鼠卵母细胞中极光蛋白激酶的基因相互作用图谱。

IF 4.6 2区 生物学 Q2 CELL BIOLOGY Frontiers in Cell and Developmental Biology Pub Date : 2024-09-25 eCollection Date: 2024-01-01 DOI:10.3389/fcell.2024.1455280
Cecilia S Blengini, Karen Schindler
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引用次数: 0

摘要

极光激酶(AURKs)是丝氨酸-苏氨酸蛋白激酶家族中对细胞分裂至关重要的一种。体细胞只表达 AURKA 和 AURKB。然而,哺乳动物生殖细胞和一些癌细胞则表达所有三种同工酶。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。我们采用了一种涉及不同极光激酶卵母细胞特异性基因敲除组合的系统遗传方法,完成了卵母细胞-极光激酶基因相互作用图谱,并表明一个极光激酶基因组拷贝对于支持雌性生育能力和卵母细胞减数分裂是必要且足够的。我们进一步证实,AURKB 和 AURKC 无法单独补偿 AURKA。这些结果突显了 AURKA 在小鼠卵母细胞中的重要性,证明它是纺锤体形成和染色体正常分离所必需的。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,但这些卵子的质量却受到了影响,这表明AURKB在调节纺锤体组装检查点或控制细胞周期方面发挥作用。结合之前的研究,我们完全确定了极光激酶之间的遗传相互作用,并强化了AURKA表达在卵母细胞减数分裂中的重要性。
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Genetic interaction mapping of Aurora protein kinases in mouse oocytes.

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.

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来源期刊
Frontiers in Cell and Developmental Biology
Frontiers in Cell and Developmental Biology Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
9.70
自引率
3.60%
发文量
2531
审稿时长
12 weeks
期刊介绍: Frontiers in Cell and Developmental Biology is a broad-scope, interdisciplinary open-access journal, focusing on the fundamental processes of life, led by Prof Amanda Fisher and supported by a geographically diverse, high-quality editorial board. The journal welcomes submissions on a wide spectrum of cell and developmental biology, covering intracellular and extracellular dynamics, with sections focusing on signaling, adhesion, migration, cell death and survival and membrane trafficking. Additionally, the journal offers sections dedicated to the cutting edge of fundamental and translational research in molecular medicine and stem cell biology. With a collaborative, rigorous and transparent peer-review, the journal produces the highest scientific quality in both fundamental and applied research, and advanced article level metrics measure the real-time impact and influence of each publication.
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