Mastl is required for timely activation of APC/C in meiosis I and Cdk1 reactivation in meiosis II

J Cell Biol. 2014 Sep 29;206(7):843-53. doi: 10.1083/jcb.201406033. Epub 2014 Sep 22.

Abstract

In mitosis, the Greatwall kinase (called microtubule-associated serine/threonine kinase like [Mastl] in mammals) is essential for prometaphase entry or progression by suppressing protein phosphatase 2A (PP2A) activity. PP2A suppression in turn leads to high levels of Cdk1 substrate phosphorylation. We have used a mouse model with an oocyte-specific deletion of Mastl to show that Mastl-null oocytes resume meiosis I and reach metaphase I normally but that the onset and completion of anaphase I are delayed. Moreover, after the completion of meiosis I, Mastl-null oocytes failed to enter meiosis II (MII) because they reassembled a nuclear structure containing decondensed chromatin. Our results show that Mastl is required for the timely activation of anaphase-promoting complex/cyclosome to allow meiosis I exit and for the rapid rise of Cdk1 activity that is needed for the entry into MII in mouse oocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anaphase
  • Anaphase-Promoting Complex-Cyclosome / metabolism*
  • Animals
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism*
  • Enzyme Induction
  • Female
  • HEK293 Cells
  • Humans
  • Male
  • Meiosis*
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Microtubule-Associated Proteins / physiology*
  • Oocytes / enzymology
  • Phosphorylation
  • Protein Phosphatase 2 / metabolism
  • Protein Processing, Post-Translational
  • Protein Serine-Threonine Kinases / physiology*
  • Single-Cell Analysis

Substances

  • Microtubule-Associated Proteins
  • Anaphase-Promoting Complex-Cyclosome
  • Protein Serine-Threonine Kinases
  • greatwall protein, mouse
  • CDC2 Protein Kinase
  • Protein Phosphatase 2