CAP1-mediated actin cycling via ADF/cofilin proteins is essential for asymmetric division in mouse oocytes

ABSTRACT Dynamic reorganization of the actin cytoskeleton is fundamental to a number of cellular events, and various actin-regulatory proteins modulate actin polymerization and depolymerization. Adenylyl cyclase-associated proteins (CAPs), highly conserved actin monomer-binding proteins, have been known to promote actin disassembly by enhancing the actin-severing activity of the ADF/cofilin protein family. In this study, we found that CAP1 regulated actin remodeling during mouse oocyte maturation. Efficient actin disassembly during oocyte maturation is essential for asymmetric division and cytokinesis. CAP1 knockdown impaired meiotic spindle migration and asymmetric division, and resulted in an accumulation of excessive actin filaments near the spindles. In contrast, CAP1 overexpression reduced actin mesh levels. CAP1 knockdown also rescued a decrease in cofilin family protein overexpression-mediated actin levels, and simultaneous expression of human CAP1 (hCAP1) and cofilin synergistically decreased cytoplasmic actin levels. Overexpression of hCAP1 decreased the amount of phosphorylated cofilin, indicating that CAP1 facilitated actin depolymerization via interaction with ADF/cofilin during mouse oocyte maturation. Taken together, our results provide evidence for the importance of dynamic actin recycling by CAP1 and cofilin in the asymmetric division of mouse female gametes. This article has an associated First Person interview with the first author of the paper. Summary: CAP1 is shown to regulate the ADF/cofilin protein family that mediates dynamic actin recycling in mouse oocytes.

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