Prophase I arrest and progression to metaphase I in mouse oocytes are controlled by Emi1-dependent regulation of APC(Cdh1).
Mammalian oocytes are arrested in prophase of the first meiotic division. Progression into the first meiotic division is driven by an increase in the activity of maturation-promoting factor (MPF). In mouse oocytes, we find that early mitotic inhibitor 1 (Emi1), an inhibitor of the anaphase-promoting complex (APC) that is responsible for cyclin B destruction and inactivation of MPF, is present at prophase I and undergoes Skp1-Cul1-F-box/betaTrCP-mediated destruction immediately after germinal vesicle breakdown (GVBD). Exogenous Emi1 or the inhibition of Emi1 destruction in prophase-arrested oocytes leads to a stabilization of cyclin B1-GFP that is sufficient to trigger GVBD. In contrast, the depletion of Emi1 using morpholino oligonucleotides increases cyclin B1-GFP destruction, resulting in an attenuation of MPF activation and a delay of entry into the first meiotic division. Finally, we show that Emi1-dependent effects on meiosis I require the presence of Cdh1. These observations reveal a novel mechanism for the control of entry into the first meiotic division: an Emi1-dependent inhibition of APC(Cdh1).
Marangos
Petros
P
Department of Physiology, University College London, London WC1E 6BT, England, UK. p.marangos@ucl.ac.uk
Verschuren
Emmy W
EW
Chen
Ruby
R
Jackson
Peter K
PK
Carroll
John
J
D016475:3T3 Cells; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism*; D019926:Cyclin B / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D044783:F-Box Proteins / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008540:Meiosis; D049469:Meiotic Prophase I; D000090204:Mesothelin; D008677:Metaphase; D051379:Mice; D009865:Oocytes / Q000166:cytology* / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
D018797:Cell Cycle Proteins; D019926:Cyclin B; C498959:Emi1 protein, mouse; D044783:F-Box Proteins; C498960:FBXO5 protein, human; C000715528:Msln protein, mouse; D011506:Proteins; D012333:RNA, Messenger; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D044843:SKP Cullin F-Box Protein Ligases; D000090204:Mesothelin