Li Meng-Xiang, Zhang Kun-Huan, Zou Yuan-Jing, Lu Ping-Shuang, Sun Shao-Chen, Wang Yue
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China.
Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi of Guangxi Higher Education Institutions, Reproductive Medicine of Guangxi Medical and Health Key Discipline Construction Project, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
FASEB J. 2025 Jul 31;39(14):e70854. doi: 10.1096/fj.202501664R.
KIF16B is a member of the kinesin-3 family of motor proteins, which facilitates processes such as vesicle transport, microtubule dynamics, and organelle function during mitosis. In this study, we explored the role of KIF16B in meiosis. Our findings indicate that KIF16B is involved in the meiotic G2-M transition and spindle assembly in oocytes. KIF16B was consistently expressed throughout the meiotic cell cycle of mouse oocytes. After the occurrence of germinal vesicle breakdown, KIF16B became concentrated on microtubules. The exhaustion of KIF16B induced the impairment of meiotic cell cycle progression, which was due to the inactivation of CDK1 and the reduction in the level of cyclin B1, consequently resulting in the failure of germinal vesicle breakdown. Furthermore, aberrant spindle phenotypes and disordered chromosome alignment were observed in KIF16B-depleted oocytes, along with improper kinetochore-microtubule attachments. These abnormal K-MT attachments resulted in the persistent activation of BubR1/Bub3 at the kinetochores. Moreover, KIF16B knockdown destabilized α-tubulin by affecting the activity of histone deacetylase 6 (HDAC6). Further analysis revealed that KIF16B participated in the Ran GTPase-dependent activation of TPX2, which in turn regulated the phosphorylation levels of Aurora A-polo-like kinase 1 (PLK1), driving the proper assembly of the spindle. In conclusion, our data indicated that KIF16B is crucial for meiosis resumption and spindle assembly in mouse oocytes.
KIF16B是驱动蛋白-3家族运动蛋白的成员之一，在有丝分裂过程中促进诸如囊泡运输、微管动力学和细胞器功能等过程。在本研究中，我们探究了KIF16B在减数分裂中的作用。我们的研究结果表明，KIF16B参与卵母细胞减数分裂的G2-M期转换和纺锤体组装。KIF16B在小鼠卵母细胞的整个减数分裂细胞周期中持续表达。生发泡破裂发生后，KIF16B集中在微管上。KIF16B的耗尽导致减数分裂细胞周期进程受损，这是由于CDK1失活和细胞周期蛋白B1水平降低，从而导致生发泡破裂失败。此外，在KIF16B缺失的卵母细胞中观察到异常的纺锤体表型和染色体排列紊乱，以及动粒-微管附着不当。这些异常的动粒-微管附着导致动粒处BubR1/Bub3持续激活。此外，KIF16B敲低通过影响组蛋白去乙酰化酶6（HDAC6）的活性使α-微管蛋白不稳定。进一步分析表明，KIF16B参与了Ran GTP酶依赖性的TPX2激活，进而调节极光激酶A-类 polo样激酶1（PLK1）的磷酸化水平，驱动纺锤体的正确组装。总之，我们的数据表明，KIF16B对小鼠卵母细胞减数分裂恢复和纺锤体组装至关重要。
