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

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.

Cofilin regulates actin network homeostasis and microvilli length in mouse oocytes

“…2A, middle), suggesting that a small pool of active cofilin is engaged in regulating nuclear Factin turnover during prophase arrest. This is consistent with the reported enrichment of cofilin in the GV nucleoplasm (Jin et al, 2020).…”

“…Cytoplasmic F-actin staining did not recover however (Fig. 3B,C), consistent with the previous observation that constitutively active cofilin dissolves the F-actin mesh (Jin et al, 2020).…”

“…Two candidates are AIP1 and coronin, which synergize with cofilin to accelerate filament severing and disassembly, while inhibiting elongation of the severed fragments (Gressin et al, 2015;Jansen et al, 2015). While AIP1 was identified in mouse oocytes, it appears dispensable for normal oocyte function (Xiao et al, 2017;Jin et al, 2020). Srv2/CAP is another highly conserved regulator of actin turnover, acting synergistically with cofilin (Kotila et al, 2019;Shekhar et al, 2019).…”

Cofilin regulates actin network homeostasis and microvilli length in mouse oocytes

“…The copyright holder for this this version posted October 15, 2021. ; https://doi.org/10.1101/2021.10.15.464498 doi: bioRxiv preprint 6 in the nucleoplasm of LIMK1-expressing GV oocytes (see Figure 2A, middle), suggesting that a small pool of active cofilin is engaged in regulating nuclear F-actin turnover during prophase arrest. This is consistent with the reported enrichment of cofilin in the GV nucleoplasm (Jin et al, 2020).…”

“…Expression of the non-phosphorylatable mutant cofilin effectively abolished microvilli overgrowth in LIMK1-expressing oocytes (Figure 3A,B and Figure 4C,D). Cytoplasmic F-actin staining did not recover however (Figure 3B,C), consistent with the previous observation that constitutively active cofilin dissolves the F-actin mesh (Jin et al, 2020).…”