Mammalian Emi2 mediates cytostatic arrest and transduces the signal for meiotic exit via Cdc20.
Fertilizable mammalian oocytes are arrested at the second meiotic metaphase (mII) by the cyclinB-Cdc2 heterodimer, maturation promoting factor (MPF). MPF is stabilized via the activity of an unidentified cytostatic factor (CSF), thereby suspending meiotic progression until fertilization. We here present evidence that a conserved 71 kDa mammalian orthologue of Xenopus XErp1/Emi2, which we term endogenous meiotic inhibitor 2 (Emi2) is an essential CSF component. Depletion in situ of Emi2 by RNA interference elicited precocious meiotic exit in maturing mouse oocytes. Reduction of Emi2 released mature mII oocytes from cytostatic arrest, frequently inducing cytodegeneration. Mos levels autonomously declined to undetectable levels in mII oocytes. Recombinant Emi2 reduced the propensity of mII oocytes to exit meiosis in response to activating stimuli. Emi2 and Cdc20 proteins mutually interact and Cdc20 ablation negated the ability of Emi2 removal to induce metaphase release. Consistent with this, Cdc20 removal prevented parthenogenetic or sperm-induced meiotic exit. These studies show in intact oocytes that the interaction of Emi2 with Cdc20 links activating stimuli to meiotic resumption at fertilization and during parthenogenesis in mammals.
Shoji
Shisako
S
Laboratory of Mammalian Molecular Embryology, RIKEN Center for Developmental Biology, Chuo-ku, Kobe, Japan.
Yoshida
Naoko
N
Amanai
Manami
M
Ohgishi
Maki
M
Fukui
Tomoyuki
T
Fujimoto
Satoko
S
Nakano
Yoshikazu
Y
Kajikawa
Eriko
E
Perry
Anthony C F
AC
D000818:Animals; D064199:Cdc20 Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D019926:Cyclin B / Q000378:metabolism; D044783:F-Box Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005306:Fertilization / Q000502:physiology; D008540:Meiosis / Q000187:drug effects / Q000502:physiology*; D000090204:Mesothelin; D008677:Metaphase / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009865:Oocytes / Q000166:cytology / Q000502:physiology*; D010312:Parthenogenesis / Q000187:drug effects / Q000502:physiology; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D064199:Cdc20 Proteins; C577491:Cdc20 protein, mouse; D018797:Cell Cycle Proteins; D019926:Cyclin B; C509434:Emi2 protein, mouse; D044783:F-Box Proteins; C000715528:Msln protein, mouse; D034741:RNA, Small Interfering; D000090204:Mesothelin