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Evaluation of the Spindle Assembly Checkpoint Integrity in Mouse Oocytes
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Evaluation of the Spindle Assembly Checkpoint Integrity in Mouse Oocytes

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PAK4 promotes the cytoskeletal organization and meiotic maturation via phosphorylating DDX17 in oocyte

Hengjie Wang1, Ming Gao2, Qing Cheng3

  • 1State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University, Nanjing, China.

Cell Communication and Signaling : CCS
|February 13, 2025
PubMed

Insights

The study reveals that PAK4 is crucial for mouse oocyte maturation and cytoskeletal organization by phosphorylating DDX17. PAK4 deficiency impairs oocyte quality, especially in diabetic conditions.

Area of Science:

  • Reproductive biology
  • Cell biology
  • Molecular genetics

Background:

  • PAK4 is known for its role in somatic cells, but its function in meiotic oocytes is unclear.
  • Oocyte maturation and meiotic apparatus are critical for female fertility.

Purpose of the Study:

  • To investigate the role and mechanism of PAK4 in mouse oocyte maturation.
  • To explore the impact of PAK4 deficiency on meiotic progression and oocyte quality.

Main Methods:

  • Investigated PAK4's function in mouse oocytes using genetic manipulation.
  • Performed mechanistic studies involving kinase substrate binding and functional screening.
  • Analyzed PAK4 protein levels in oocytes from diabetic mice.
  • Utilized a DDX17 mutant (DDX17-S597D) to assess the impact of phosphorylation.

Main Results:

  • PAK4 deficiency significantly disrupts meiotic progression and the meiotic apparatus in mouse oocytes.
  • PAK4 promotes cytoskeletal organization and oocyte maturation via DDX17 phosphorylation at serine 597.
  • PAK4 protein levels are reduced in oocytes from diabetic mice.
  • Expression of DDX17-S597D partially rescues meiotic defects in diabetic oocytes.

Conclusions:

  • PAK4 plays a pivotal role in oocyte development, controlling meiotic progression and structure.
  • Decreased DDX17 phosphorylation due to PAK4 insufficiency contributes to impaired oocyte quality, particularly in diabetes.
  • This study uncovers a novel mechanism regulating meiotic progression in oocytes.
Keywords:
CytoskeletonMeiosisOocytePAK4Reproduction

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