SYMPK interacts with KIF20A and NUMA1 to coordinate spindle organization and safeguard oocyte meiotic maturation

Bei Chen; Mofan Zhou; Jiaqi Wang; Jinxin Xiao; Yirong Chen; Jinying Wang; Wenlin He; Tianbao Song; Jin Luo; Qingzhen Xie; Cong Liu

doi:10.1016/j.jgg.2026.01.002

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SYMPK interacts with KIF20A and NUMA1 to coordinate spindle organization and safeguard oocyte meiotic maturation

doi: 10.1016/j.jgg.2026.01.002

a. Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China;
b. Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, Hubei 430060, China;
c. Key Laboratory of Organ Regeneration and Reconstruction, State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China;
d. Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China

Funds:

This work was supported by the Fundamental Research Funds for the Central Universities (2042024YXB002 to J. L. and 2042023kf0023 to C. L.), the National Natural Science Foundation of China (82471636 to J. L., 82471669 to Q.-Z.X., and 82301868 to C. L.), the United Fund of Hubei Province (220172269 to C. L.), and the Key Research and Development Program of Hubei Province (2021BCA107 to Q.-Z.X.). The authors thank Prof. Shuiqiao Yuan for generously providing the experimental platform that supported this work, and Prof. Mengcheng Luo for kindly providing the conditional knockout mouse model. Graphical abstract was created with BioRender.com and includes BioRender-provided elements (protein, chromosome, and traffic light icons). Created in BioRender. Chen, C. (2025) https://BioRender.com/eepesum.

Received Date: 2025-10-26
Accepted Date: 2026-01-05
Rev Recd Date: 2026-01-03

Available Online: 2026-01-10

Abstract

Abstract

Mammalian oocyte maturation relies on the precise assembly of the acentrosomal spindle, and its disruption causes aneuploidy and developmental failure. Symplekin (SYMPK), a 3′-end processing scaffold with emerging functions in regulating chromosome dynamics, remains unexplored in oocytes. Here, we investigate whether SYMPK governs spindle dynamics and chromosome fidelity during meiotic maturation. We find SYMPK dynamically tracks spindle microtubules during oocyte maturation following germinal vesicle breakdown (GVBD). By generating oocyte-specific Sympk knockout mice, loss of SYMPK in oocytes yields complete female infertility and impaired oocyte quality. Sympk-deficient oocytes show a predominant metaphase I (MI) arrest, accompanied by disorganized spindle architecture and destabilized kinetochore-microtubule attachments. Furthermore, chromosome spreads indicate persistent spindle assembly checkpoint (SAC) activation, and pharmacologic SAC inhibition can partially restore meiotic progression but not spindle integrity in SYMPK-deficient oocytes. Mechanistically, immunoprecipitation-mass spectrometry in MI oocytes reveals that SYMPK interacts with the spindle regulators KIF20A and NUMA1, and is required for their proper localization to the spindle. Collectively, these findings establish that SYMPK supports KIF20A and NUMA1 to coordinate acentrosomal spindle organization, thereby safeguarding oocyte meiotic maturation and ensuring faithful female meiotic progression.
- Oocyte,
- Meiosis,
- SYMPK,
- Spindle organization,
- Female fertility

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