CDC14B acts through FZR1 (CDH1) to prevent meiotic maturation of mouse oocytes

Karen Schindler, Richard M. Schultz

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Meiotic maturation in oocytes is a prolonged process that is unique because of cell cycle arrests at prophase of meiosis I (MI) and at metaphase of meiosis II (MII). Fluctuations in cyclin- dependent kinase 1 (CDK1/CDC2A) activity govern meiotic progression, yet little is known about how these fluctuations are achieved. CDC14 is a highly conserved dual-specificity phos- phatase that counteracts the function of proteins phosphorylated by CDK. Mammals contain two CDC14 homologs, CDC14A and CDC14B. We report that CDC14B localizes with the meiotic spindle in mouse oocytes, and (unlike somatic cells) it does not localize in the nucleolus. Oocytes that overexpress CDC14B are significantly delayed in resuming meiosis and fail to progress to MII, whereas oocytes depleted of CDC14B spontaneously resume meiosis under conditions that normally inhibit meiotic resumption. Depletion of FZR1 (CDH1), a regulatory subunit of the anaphase-promoting complex/cyclosome that targets cyclin B1 (CCNB1) for ubiquitin-mediated proteolysis, partially restores normal timing of meiotic resumption in oocytes with excess CDC14B. These studies also reveal that experimentally altering CDC14B levels generates eggs with abnormal spindles and with chromosome alignment perturbations. Our data indicate that CDC14B is a negative regulator of meiotic resumption and may regulate MI in mouse oocytes.

Original languageEnglish (US)
Pages (from-to)795-803
Number of pages9
JournalBiology of reproduction
Volume80
Issue number4
DOIs
StatePublished - Apr 2009
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Cell Biology

Keywords

  • CDC14
  • CDH1
  • Cell cycle
  • Gamete biology
  • Meiosis
  • Oocyte
  • Phosphatases

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