Aurora-C kinase deficiency causes cytokinesis failure in meiosis I and production of large polyploid oocytes in mice.
Aurora-C kinase deficiency causes cytokinesis failure in meiosis I and production of large polyploid oocytes in mice.
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DOI：
10.1091/mbc.e10-02-0170
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发表时间：
2010-07-15
影响因子：
3.3
通讯作者：
Tang TK
中科院分区：
文献类型：
--
作者：
Yang KT;Li SK;Chang CC;Tang CJ;Lin YN;Lee SC;Tang TK
我们首次报道了内源性Aurora-C的亚细胞定位，并研究了其在雌性小鼠减数分裂过程中的作用。在注射激酶缺陷型Aurora-C mRNA的卵母细胞中观察到的最显著的影响是减数分裂I中的胞质分裂失败，导致产生大的多倍体卵母细胞。我们以前分离Aurora-C/Aie 1在小鼠精子和卵子中表达的激酶的屏幕。在这里，我们显示内源性Aurora-C的本地化，并检查其在雌性小鼠减数分裂过程中的作用。Aurora-C在前中期I-中期I的着丝粒和沿着染色体臂检测到，在中期II集中在着丝粒，其中Aurora-C也在Thr 171处磷酸化。在后期I-末期I过渡期间，Aurora-C被去磷酸化并重新定位于中间区和中间体。将激酶缺陷型Aurora-C（AurC-KD）mRNA显微注射到小鼠卵母细胞中可显著抑制Aurora-C活性，并导致多种缺陷，包括染色体错位、异常的着丝粒-微管附着、染色体过早分离和减数分裂I中的胞质分裂失败。此外，AurC-KD减少Aurora-C和组蛋白H3磷酸化，并抑制Bub 1和BubR 1的动粒定位。在注射INCNEP-delIN mRNA的卵母细胞中也观察到类似的效果，其中Aurora-C结合基序被去除。在AurC-KD注射的卵母细胞中观察到的最显著的效果是减数分裂I中的胞质分裂失败，导致产生大的多倍体卵母细胞，这是一种类似于Aurora-C缺乏的人精子的模式。令人惊讶的是，我们在小鼠卵母细胞中没有检测到Aurora-B蛋白。我们建议，极光-C，而不是极光-B，在雌性小鼠减数分裂中起着至关重要的作用。
We report for the first time the subcellular localization of endogenous Aurora-C and examine its roles during female mouse meiosis. The most dramatic effect observed in the oocyte injected with kinase-deficient Aurora-C mRNA is cytokinesis failure in meiosis I, resulting in production of large polyploid oocytes. We previously isolated Aurora-C/Aie1 in a screen for kinases expressed in mouse sperm and eggs. Here, we show the localization of endogenous Aurora-C and examine its roles during female mouse meiosis. Aurora-C was detected at the centromeres and along the chromosome arms in prometaphase I–metaphase I and was concentrated at centromeres at metaphase II, in which Aurora-C also was phosphorylated at Thr171. During the anaphase I–telophase I transition, Aurora-C was dephosphorylated and relocalized to the midzone and midbody. Microinjection of the kinase-deficient Aurora-C (AurC-KD) mRNA into mouse oocytes significantly inhibited Aurora-C activity and caused multiple defects, including chromosome misalignment, abnormal kinetochore–microtubule attachment, premature chromosome segregation, and cytokinesis failure in meiosis I. Furthermore, AurC-KD reduced Aurora-C and histone H3 phosphorylation and inhibited kinetochore localization of Bub1 and BubR1. Similar effects also were observed in the oocytes injected with INCNEP-delIN mRNAs, in which the Aurora-C binding motif was removed. The most dramatic effect observed in AurC-KD–injected oocytes is cytokinesis failure in meiosis I, resulting in producing large polyploid oocytes, a pattern similar to Aurora-C deficiency human spermatozoa. Surprisingly, we detected no Aurora-B protein in mouse oocytes. We propose that Aurora-C, but not Aurora-B, plays essential roles in female mouse meiosis.
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