PAK4 Regulates Actin and Microtubule Dynamics during Meiotic Maturation in Mouse Oocyte

Int J Biol Sci. 2019 Sep 7;15(11):2408-2418. doi: 10.7150/ijbs.34718. eCollection 2019.

Abstract

Meiotic maturation of oocyte is an important process for successful fertilization, in which cytoskeletal integrality takes a significant role. The p-21 activated kinases (PAKs) belong to serine/threonine kinases that affect wide range of processes that are crucial for cell motility, survival, cell cycle, and proliferation. In this study, we used a highly selective inhibitor of PAK4, PF-3758309, to investigate the functions of PAK4 during meiotic maturation of mouse oocytes. We found that PAK4 inhibition resulted in meiotic arrest by inducing abnormal microfilament and microtubule dynamics. PAK4 inhibition impaired the microtubule stability and led to the defective kinetochore-microtubule (K-M) attachment which inevitably resulted in aneuploidy. Also, PAK4 inhibition induced abnormal acentriolar centrosome assembly during meiotic maturation. In conclusion, all these combined results suggest that PAK4 is necessary for the oocyte meiosis maturation as a regulator of cytoskeleton.

Keywords: PAK4; centrosome.; cytoskeleton; meiosis; oocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Animals
  • Centrosome / drug effects
  • Centrosome / metabolism
  • Chromosome Segregation / drug effects
  • Female
  • Kinetochores / drug effects
  • Kinetochores / metabolism
  • Meiosis / drug effects*
  • Mice
  • Microtubules / drug effects*
  • Microtubules / metabolism*
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Pyrazoles / pharmacology
  • Pyrroles / pharmacology
  • p21-Activated Kinases / antagonists & inhibitors
  • p21-Activated Kinases / metabolism*

Substances

  • Actins
  • PF 3758309
  • Pyrazoles
  • Pyrroles
  • Pak4 protein, mouse
  • p21-Activated Kinases