FKBP25 Regulates Meiotic Apparatus During Mouse Oocyte Maturation.

FKBP25 Regulates Meiotic Apparatus During Mouse Oocyte Maturation.
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FKBP25 在小鼠卵母细胞成熟过程中调节减数分裂装置

DOI:
10.3389/fcell.2021.625805
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发表时间:
2021
影响因子:
5.5
通讯作者:
Wang Q
Wang Q
中科院分区:
生物学2区
文献类型:
--
作者:
Wang D;Sun H;Zhang J;Huang Z;Li C;Han L;Xin Y;Tang S;Ge J;Wang Q

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FK506结合蛋白25(FKBP25)已被证明在有丝分裂中的核糖体生物发生、染色质组织和微管稳定性中起作用。然而,尚未研究FKBP 25在卵母细胞成熟中的作用。在这里,我们报告说,卵母细胞与FKBP25耗尽显示异常纺锤体组装和染色体排列,有缺陷的着丝粒微管附件。与该发现一致,在FKBP 25耗尽的卵母细胞中非整倍体发生率也升高。重要的是,FKBP25蛋白在衰老卵母细胞中的水平显著降低,并且FKBP25的异位表达可以部分地挽救衰老相关的减数分裂缺陷。此外,通过采用位点特异性诱变,我们确定丝氨酸163是一个主要的,如果不是唯一的,磷酸化位点调节FKBP25的减数分裂成熟的行动。总之,我们的数据表明FKBP 25是决定卵母细胞质量的关键因素,并可能介导母体衰老对女性生殖的影响。
FK506 binding proteins 25 (FKBP25) has been shown to function in ribosome biogenesis, chromatin organization, and microtubule stability in mitosis. However, the role of FKBP25 in oocyte maturation has not been investigated. Here, we report that oocytes with FKBP25 depletion display abnormal spindle assembly and chromosomes alignment, with defective kinetochore-microtubule attachment. Consistent with this finding, aneuploidy incidence is also elevated in oocytes depleted of FKBP25. Importantly, FKBP25 protein level in old oocytes is significantly reduced, and ectopic expression of FKBP25 could partly rescue the aging-associated meiotic defects. In addition, by employing site-specific mutagenesis, we identify that serine 163 is a major, if not unique, phosphorylation site modulating the action of FKBP25 on meiotic maturation. In summary, our data indicate that FKBP25 is a pivotal factor for determining oocyte quality, and may mediate the effects of maternal aging on female reproduction.
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