AIP1 and Cofilin control the actin dynamics to modulate the asymmetric division and cytokinesis in mouse oocytes

FASEB J. 2020 Aug;34(8):11292-11306. doi: 10.1096/fj.202000093R. Epub 2020 Jun 30.

Abstract

Actin-interacting protein 1 (AIP1), also known as WD repeat-containing protein 1 (WDR1), is ubiquitous in eukaryotic organisms, and it plays critical roles in the dynamic reorganization of the actin cytoskeleton. However, the biological function and mechanism of AIP1 in mammalian oocyte maturation is still largely unclear. In this study, we demonstrated that AIP1 boosts ADF/Cofilin activity in mouse oocytes. AIP1 is primarily distributed around the spindle region during oocyte maturation, and its depletion impairs meiotic spindle migration and asymmetric division. The knockdown of AIP1 resulted in the gathering of a large number of actin-positive patches around the spindle region. This effect was reduced by human AIP1 (hAIP1) or Cofilin (S3A) expression. AIP1 knockdown also reduced the phosphorylation of Cofilin near the spindle, indicating that AIP1 interacts with ADF/Cofilin-decorated actin filaments and enhances filament disassembly. Moreover, the deletion of AIP1 disrupts Cofilin localization in metaphase I (MI) and induces cytokinesis defects in metaphase II (MII). Taken together, our results provide evidence that AIP1 promotes actin dynamics and cytokinesis via Cofilin in the gametes of female mice.

Keywords: ADF/Cofilin; AIP1; actin; oocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actin Depolymerizing Factors / metabolism*
  • Actins / metabolism
  • Animals
  • Cells, Cultured
  • Cytokinesis / physiology*
  • Female
  • Humans
  • Metaphase / physiology*
  • Mice
  • Mice, Inbred ICR
  • Oocytes / metabolism*
  • Phosphorylation / physiology
  • Spindle Apparatus / metabolism
  • ras GTPase-Activating Proteins / metabolism*

Substances

  • Actin Depolymerizing Factors
  • Actins
  • Dab2ip protein, mouse
  • ras GTPase-Activating Proteins