Successive recruitment of p-CDC25B-Ser351 and p-cyclin B1-Ser123 to centrosomes contributes to the release of mouse oocytes from prophase I arrest.

Background: The molecular mechanism that controls the activation of Cyclin B1-CDK1 complex has been widely investigated. It is generally believed that CDC25B acts as a starter phosphatase of mitosis. In this study, we investigate the sequential regulation of meiotic resumption by CDC25B and Cyclin B1 in mouse oocytes. Results Injection of mRNAs coding for CDC25B-Ser351A and/or Cyclin B1-Ser123A shows a more potent maturation-inhibiting ability than their respective wild type. Co-injection of mRNAs coding for phosphor-mimic CDC25B-Ser351D and Cyclin B1-Ser123D can rescue this prophase I arrest induced by CDC25B-Ser351A or Cyclin B1-Ser123A. In addition, p-CDC25B-Ser351 is co-localized at the microtubule-organizing centers (MTOCs) with Aurora kinase A (AURKA) during maturation and p-Cyclin B1-Ser123 is only captured on MTOCs shortly before germinal vesicle breakdown (GVBD). Depletion of AURKA not only resulted in metaphase I (MI) spindle defects and anaphase I (AI) abnormal chromosomes separation but also prevented the phosphorylation of CDC25B-Ser351 at centrosomes. AURKA depletion induced deficiencies of spindle assembly and progression to MII can be rescued by CDC25B-Ser351D mRNA injection. AURKA induced phosphorylation and recruitment of CDC25B to MTOCs prior to p-Cyclin B1-Ser123, and this sequential regulation is essential for the commitment of the oocytes to resume meiosis. Developmental Dynamics 244:110-121, 2015. (c) 2014 Wiley Periodicals, Inc. Key Findings