Department of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 440-746, Korea.
Division of Radiation Cancer Research, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
Histochem Cell Biol. 2019 Sep;152(3):207-215. doi: 10.1007/s00418-019-01800-9. Epub 2019 Jun 27.
Faithful chromosome segregation during the cell cycle is ensured by the spindle assembly checkpoint (SAC). Although SAC activity is highly conserved and most organisms share common SAC components, additional proteins that regulate SAC activity to ensure high fidelity chromosome segregation are present in higher eukaryotes. Zw10 is one of these additional SAC components. Although Zw10 has been demonstrated to be involved in SAC activity during mitosis, little is known about its role during oocyte meiosis. Here, we report that Zw10 is localized at the kinetochore and is required for SAC activation during meiotic maturation. Knockdown of Zw10 led to precocious polar body extrusion by impairing Mad2 recruitment at kinetochores. Moreover, Zw10 knockdown impaired chromosome alignment and kinetochore-microtubule attachment, increasing the incidence of aneuploidy. Furthermore, Zw10 expression decreased with maternal age, suggesting that Zw10 is associated with the age-related increase in the incidence of aneuploidy. Together, our results demonstrate that Zw10 is localized at kinetochores and functions as an essential SAC component in mouse oocytes.
细胞周期中染色体的正确分离是由纺锤体组装检查点（SAC）来保证的。尽管 SAC 活性高度保守，大多数生物共享共同的 SAC 成分，但在高等真核生物中存在额外的蛋白质来调节 SAC 活性以确保高保真度的染色体分离。Zw10 就是这些额外的 SAC 成分之一。尽管已经证明 Zw10 在有丝分裂过程中参与 SAC 活性，但对其在卵母细胞减数分裂中的作用知之甚少。在这里，我们报告 Zw10 定位于动粒上，并且在减数成熟过程中 SAC 的激活是必需的。Zw10 的敲低导致极体过早排出，因为它损害了 Mad2 在动粒上的募集。此外，Zw10 的敲低会影响染色体的排列和动粒-微管的附着，从而增加非整倍体的发生率。此外，Zw10 的表达随母体年龄的增加而降低，这表明 Zw10 与非整倍体发生率随年龄增加有关。总之，我们的结果表明，Zw10 定位于动粒上，并作为小鼠卵母细胞中必不可少的 SAC 成分发挥作用。
