Article
- The EMBO Journal (2006) 25, 834 - 845
- doi:10.1038/sj.emboj.7600953
Published online: 2 February 2006
Subject Categories:
Mammalian Emi2 mediates cytostatic arrest and transduces the signal for meiotic exit via Cdc20
Shisako Shoji, Naoko Yoshida, Manami Amanai, Maki Ohgishi, Tomoyuki Fukui, Satoko Fujimoto, Yoshikazu Nakano, Eriko Kajikawa and Anthony C F Perry
- Laboratory of Mammalian Molecular Embryology, RIKEN Center for Developmental Biology, Chuo-ku, Kobe, Japan
Correspondence to:
Anthony C F Perry, Laboratory of Mammalian Molecular Embryology, RIKEN Center for Developmental Biology, 2-2-3 Minatojima Minamimachi, Chuo-ku, Kobe 650-0047, Japan. Tel.: +81 78 306 3054; Fax: +81 78 306 3144; E-mail: tony@cdb.riken.jp
Received 29 August 2005; Accepted 8 December 2005
Abstract
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.
Keywords:
- cytostatic factor,
- fertilization,
- metaphase II oocyte,
- RNAi,
- XErp1/Emi2
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