Selective disruption of aurora C kinase reveals distinct functions from aurora B kinase during meiosis in mouse oocytes.
Selective disruption of aurora C kinase reveals distinct functions from aurora B kinase during meiosis in mouse oocytes.
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DOI：
10.1371/journal.pgen.1004194
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发表时间：
2014-02
期刊：
影响因子：
4.5
通讯作者：
Schindler K
中科院分区：
文献类型：
--
作者：
Balboula AZ;Schindler K
极光B激酶（AURKB）是染色体乘客复合体（CPC）的催化亚基，是染色体分离的重要调节因子。在有丝分裂中，CPC需要调节着丝点微管（K-MT）附着，纺锤体组装检查点和细胞质分裂。生殖细胞表达AURKB的同源物AURKC，它也可以在CPC中发挥作用。传统方法在卵母细胞减数分裂过程中分离AURKB和AURKC功能尚未成功。因此，AURKC的减数分裂功能尚不完全清楚。在这里，我们描述了一个atp结合口袋- aurkc突变体，当在小鼠卵母细胞中表达时，特异性地干扰AURKC-CPC而不是AURKB-CPC功能。利用这个突变体，我们首次发现AURKC具有与AURKB不重叠的功能。这些功能包括调节局部CPC活性，调节减数分裂中期染色体排列和K-MT附着。我们发现，在减数分裂过程中，AURKC-CPC并不是唯一调节纺锤体组装检查点的CPC复合体，因此大多数受AURKC干扰的卵母细胞在Met i处停滞。一小部分卵母细胞确实正常地进行细胞质分裂，这表明AURKC-CPC并不是末期i的唯一CPC复合体。但是，由此产生的卵是非整倍体的，这表明AURKC是女性配子中减数分裂染色体分离的关键调节因子。综上所述，这些数据表明哺乳动物卵母细胞含有AURKC，可以有效地进行减数分裂I，并确保有性生殖所需的高质量卵子。精确控制染色体分离是产生具有适当染色体数目的细胞的必要条件。在生殖细胞、精子和卵子中，染色体数目异常会导致不孕、流产，或者在活产的情况下，导致发育障碍，如唐氏综合症。由于不完全清楚的原因，卵子比精子更容易发生染色体分离错误。在这项研究中，我们研究了染色体分离的调节因子Aurora C激酶在小鼠卵母细胞中的作用。这是首次将其功能与序列高度相似的Aurora B激酶分离开来的研究。我们发现极光C是唯一需要产生具有适当数量染色体的卵子的。
Aurora B kinase (AURKB) is the catalytic subunit of the chromosomal passenger complex (CPC), an essential regulator of chromosome segregation. In mitosis, the CPC is required to regulate kinetochore microtubule (K-MT) attachments, the spindle assembly checkpoint, and cytokinesis. Germ cells express an AURKB homolog, AURKC, which can also function in the CPC. Separation of AURKB and AURKC function during meiosis in oocytes by conventional approaches has not been successful. Therefore, the meiotic function of AURKC is still not fully understood. Here, we describe an ATP-binding-pocket-AURKC mutant, that when expressed in mouse oocytes specifically perturbs AURKC-CPC and not AURKB-CPC function. Using this mutant we show for the first time that AURKC has functions that do not overlap with AURKB. These functions include regulating localized CPC activity and regulating chromosome alignment and K-MT attachments at metaphase of meiosis I (Met I). We find that AURKC-CPC is not the sole CPC complex that regulates the spindle assembly checkpoint in meiosis, and as a result most AURKC-perturbed oocytes arrest at Met I. A small subset of oocytes do proceed through cytokinesis normally, suggesting that AURKC-CPC is not the sole CPC complex during telophase I. But, the resulting eggs are aneuploid, indicating that AURKC is a critical regulator of meiotic chromosome segregation in female gametes. Taken together, these data suggest that mammalian oocytes contain AURKC to efficiently execute meiosis I and ensure high-quality eggs necessary for sexual reproduction. Precise control of chromosome segregation is essential for generating cells with the proper number of chromosomes. In germ cells, sperm and egg, an abnormal chromosome number leads to infertility, miscarriage, or, in the case of a live birth, developmental disorders such as Down Syndrome. For reasons not entirely clear, eggs are more prone to chromosome segregation mistakes than sperm. In this study, we study the role of a regulator of chromosome segregation, Aurora C kinase, in mouse oocytes. This is the first study to separate its function from Aurora B kinase that is highly similar in sequence. We find Aurora C is uniquely required to produce eggs with the proper number of chromosomes.
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7.5
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DOI：
10.1073/pnas.1111239108
发表时间：
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影响因子：
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作者：
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DOI：
10.1083/jcb.201303019
发表时间：
2013-07-22
期刊：
The Journal of cell biology
影响因子：
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作者：
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通讯作者：
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