Wee1B, Myt1, and Cdc25 function in distinct compartments of the mouse oocyte to control meiotic resumption.
After a long period of quiescence at dictyate prophase I, termed the germinal vesicle (GV) stage, mammalian oocytes reenter meiosis by activating the Cdc2-cyclin B complex (maturation-promoting factor [MPF]). The activity of MPF is regulated by Wee1/Myt1 kinases and Cdc25 phosphatases. In this study, we demonstrate that the sequestration of components that regulate MPF activity in distinct subcellular compartments is essential for their function during meiosis. Down-regulation of either Wee1B or Myt1 causes partial meiotic resumption, and oocytes reenter the cell cycle only when both proteins are down-regulated. Shortly before GV breakdown (GVBD), Cdc25B is translocated from the cytoplasm to the nucleus, whereas Wee1B is exported from the nucleus to the cytoplasm. These movements are regulated by PKA inactivation and MPF activation, respectively. Mislocalized Wee1B or Myt1 is not able to maintain meiotic arrest. Thus, cooperation of Wee1B, Myt1, and Cdc25 is required to maintain meiotic arrest and relocation of these components before GVBD is necessary for meiotic reentry.
Oh
Jeong Su
JS
Department of Obstetrics, Gynecology, and Reproductive Sciences, Center for Reproductive Sciences, University of California, San Francisco, San Francisco, CA 94143, USA.
Han
Seung Jin
SJ
Conti
Marco
M
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D002451:Cell Compartmentation / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D016200:Maturation-Promoting Factor / Q000235:genetics / Q000378:metabolism; D008540:Meiosis / Q000502:physiology*; D000090204:Mesothelin; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes / Q000378:metabolism* / Q000648:ultrastructure; D021381:Protein Transport / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D020687:cdc25 Phosphatases / Q000235:genetics / Q000378:metabolism*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C000715528:Msln protein, mouse; C489726:Myt1 protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; C499348:Wee1 protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases; D016200:Maturation-Promoting Factor; C517006:Cdc25b protein, mouse; D020687:cdc25 Phosphatases; D000090204:Mesothelin