Guo Jia-Ni, Zhu Liu, Meng Tie-Gang, Zhang Yi-Na, Sun Si-Min, Yang Xue-Mei, Zhao Bing-Wang, Lu Yi-Ke, Xu Yuan-Hong, Yue Wei, Han Zhiming, Wong Catherine C L, Wang Zhen-Bo
State Key Laboratory of Organ Regeneration and Reconstruction, Institute of Zoology, Chinese Academy of Sciences, #Beichen West Rd, Chaoyang, Beijing, 100101, China.
Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, 100101, China.
Cell Mol Life Sci. 2025 Jul 30;82(1):292. doi: 10.1007/s00018-025-05821-7.
Meiotic spindle is an intricate structure and required for chromosome segregation and the proper meiotic progression during oocyte maturation, and its function is regulated by a complex network of proteins located at spindle and its peripheral region. However, proteome of meiotic spindle remains poorly characterized. Here, we acquired the proteomic profile of spindles isolated from metaphase I (MI) and metaphase II (MII) mouse oocytes. In particular, we identified Ccdc69 as a novel regulator of spindle assembly in mouse oocytes. Although deletion of Ccdc69 did not affect female fertility, the MI spindles were elongated in Ccdc69 knockout oocytes. Overexpression of Ccdc69 induced spindle defects by reducing microtubule formation and disturbing acentriolar microtubule organization centers (aMTOCs) distribution. Furthermore, Ccdc69 overexpression impaired kinetochore-microtubule (K-MT) attachment and delayed meiotic progression by abnormal activation of spindle assembly checkpoint (SAC). Taken together, our study depicts the proteome of spindles during mouse oocyte maturation and demonstrates that Ccdc69 regulates spindle assembly and meiotic progression the way similar to "The Tightening Spell of Sun Wukong's Golden Headband" in the famous Chinese Classic Journey to the West.
减数分裂纺锤体是一种复杂的结构，在卵母细胞成熟过程中对染色体分离和减数分裂的正常进程至关重要，其功能由位于纺锤体及其周边区域的复杂蛋白质网络调节。然而，减数分裂纺锤体的蛋白质组仍然缺乏充分的表征。在这里，我们获得了从处于中期I（MI）和中期II（MII）的小鼠卵母细胞中分离出的纺锤体的蛋白质组图谱。特别地，我们鉴定出Ccdc69是小鼠卵母细胞纺锤体组装的一种新型调节因子。虽然缺失Ccdc69并不影响雌性生育能力，但在Ccdc69基因敲除的卵母细胞中，MI纺锤体拉长。过表达Ccdc69会通过减少微管形成和扰乱无中心粒微管组织中心（aMTOCs）分布来诱导纺锤体缺陷。此外，Ccdc69过表达会损害动粒微管（K-MT）附着，并通过异常激活纺锤体组装检查点（SAC）延迟减数分裂进程。综上所述，我们的研究描绘了小鼠卵母细胞成熟过程中纺锤体的蛋白质组，并证明Ccdc69以类似于中国著名古典小说《西游记》中“孙悟空金箍紧箍咒”的方式调节纺锤体组装和减数分裂进程。
