Stag3 regulates microtubule stability to maintain euploidy during mouse oocyte meiotic maturation

Oncotarget. 2017 Jan 3;8(1):1593-1602. doi: 10.18632/oncotarget.13684.

Abstract

Stag3, a meiosis-specific subunit of cohesin complex, has been demonstrated to function in both male and female reproductive systems in mammals. However, its roles during oocyte meiotic maturation have not been fully defined. In the present study, we report that Stag3 uniquely accumulates on the spindle apparatus and colocalizes with microtubule fibers during mouse oocyte meiotic maturation. Depletion of Stag3 by gene-targeting morpholino disrupts normal spindle assembly and chromosome alignment in oocytes. We also find that depletion of Stag3 reduces the acetylated level of tubulin and microtubule resistance to microtubule depolymerizing drug, suggesting that Stag3 is required for microtubule stability. Consistent with these observations, kinetochore-microtubule attachment, an important mechanism controlling chromosome alignment, is severely impaired in Stag3-depleted oocytes, resultantly causing the significantly increased incidence of aneuploid eggs. Collectively, our data reveal that Stag3 is a novel regulator of microtubule dynamics to ensure euploidy during moue oocyte meiotic maturation.

Keywords: Stag3; aneuploid egg; chromosome alignment; microtubule stability; spindle assembly.

MeSH terms

  • Aneuploidy*
  • Animals
  • Cell Cycle Proteins / metabolism
  • Chromosomal Proteins, Non-Histone / metabolism
  • Chromosome Segregation / genetics*
  • Cohesins
  • Female
  • Gene Knockdown Techniques
  • Kinetochores / physiology
  • M Phase Cell Cycle Checkpoints / genetics
  • Meiosis / physiology*
  • Mice
  • Mice, Inbred ICR
  • Microtubules / physiology*
  • Morpholinos / genetics
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Oocytes / growth & development*
  • Spindle Apparatus / physiology*
  • Tubulin / metabolism
  • Tubulin Modulators / pharmacology

Substances

  • Cell Cycle Proteins
  • Chromosomal Proteins, Non-Histone
  • Morpholinos
  • Nuclear Proteins
  • Stag3 protein, mouse
  • Tubulin
  • Tubulin Modulators