Okadaic acid and p13suc1 modulate the reinitiation of meiosis in mouse oocytes.
Short-term exposure to okadaic acid (OA), a specific inhibitor of protein phosphatases 1 and 2A, induced resumption of meiosis, including metaphase spindle formation, in mouse oocytes treated with a phosphodiesterase inhibitor, while long incubations with OA arrested oocyte maturation at a step prior to spindle formation. To explore the basis for this difference, the overall patterns of protein synthesis and phosphorylation and the production of tissue-type plasminogen activator (tPA), the synthesis of which is induced after germinal vesicle breakdown (GVBD), were analyzed under various OA treatments. Short-term exposure to OA led to tPA production and did not greatly affect the maturation-associated changes in protein phosphorylation. By contrast, a long application of OA did not result in tPA production and induced more marked changes in protein phosphorylation. Microinjection into prophase oocytes of the product of the fission yeast gene p13suc1, known to inhibit p34cdc2 kinase activation and/or activity, prevented meiotic reinitiation. This effect was overcome by microinjection of OA, at concentrations higher than those required for induction of maturation in the absence of p13suc1. These observations suggest that inhibition of phosphatase 1 or 2A or both triggers meiotic resumption by acting at the same site or at a site proximal to the p13suc1-sensitive step of cdc2 kinase activation.
Gavin
A C
AC
Department of Obstetrics and Gynaecology, Hôpital Cantonal Universitaire, Geneva, Switzerland.
Vassalli
J D
JD
Cavadore
J C
JC
Schorderet-Slatkine
S
S
D000818:Animals; D018797:Cell Cycle Proteins; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005260:Female; D005656:Fungal Proteins / Q000494:pharmacology*; D066298:In Vitro Techniques; D016200:Maturation-Promoting Factor / Q000378:metabolism; D008540:Meiosis / Q000187:drug effects* / Q000502:physiology; D008677:Metaphase / Q000187:drug effects; D051379:Mice; D019319:Okadaic Acid; D009865:Oocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009866:Oogenesis / Q000187:drug effects; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D054645:Protein Phosphatase 1; D012333:RNA, Messenger / Q000235:genetics; D029702:Schizosaccharomyces pombe Proteins; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics
D018797:Cell Cycle Proteins; D004988:Ethers, Cyclic; D005656:Fungal Proteins; D012333:RNA, Messenger; D029702:Schizosaccharomyces pombe Proteins; C051655:Suc1 protein, S pombe; D019319:Okadaic Acid; D016200:Maturation-Promoting Factor; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D010959:Tissue Plasminogen Activator