2. Academic Validation
  3. SYMPK interacts with KIF20A and NUMA1 to coordinate spindle organization and safeguard oocyte meiotic maturation

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

  • J Genet Genomics. 2026 Jan 9:S1673-8527(26)00002-0. doi: 10.1016/j.jgg.2026.01.002.
Bei Chen 1,  Mofan Zhou 2,  Jiaqi Wang 3,  Jinxin Xiao 3,  Yirong Chen 3,  Jinying Wang 3,  Wenlin He 4,  Tianbao Song 4,  Jin Luo 5,  Qingzhen Xie 6,  Cong Liu 7
Affiliations

Affiliations

  • 1 Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China; Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, Hubei 430060, China.
  • 2 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.
  • 3 Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
  • 4 Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
  • 5 Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China; Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, Hubei 430060, China. Electronic address: [email protected].
  • 6 Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China; Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, Hubei 430060, China. Electronic address: [email protected].
  • 7 Reproductive Medical Center, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China; Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, Hubei 430060, China. Electronic address: [email protected].
PMID: 41520922 DOI: 10.1016/j.jgg.2026.01.002
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.

Keywords

Female fertility; Meiosis; Oocyte; SYMPK; Spindle organization.

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