Pleiotropic effect of okadaic acid on maturing mouse oocytes.
Okadaic acid (OA), a potent inhibitor of types 1 and 2A protein phosphatases, was shown recently to induce chromatin condensation and germinal vesicle breakdown (GVBD) in mouse oocytes arrested at the dictyate stage by dibutyryl cAMP (dbcAMP), isobutyl methylxanthine (IBMX) and 12,13-phorbol dibutyrate (PDBu). We confirm these results using IBMX and another phorbol diester, 12-O-tetradecanoylphorbol-13-acetate (TPA) and show that OA also bypasses the inhibitory effect of 6-dimethylaminopurine (6-DMAP). It has been concluded that protein phosphatases 1 and/or 2A (PP1, 2A), involved in the negative control of MPF activation, are thus operating downstream from both the protein kinase A and protein kinase C catalysed phosphorylation steps that prevent the breakdown of GV. Similar enzymatic activities are also able to counteract the general inhibition of protein phosphorylation. However, PP1 and/or PP2A are positively involved in the activation of pericentriolar material (PCM) into microtubule organizing centres (MTOCs). This explains the inhibitory effect of OA on spindle assembly. Finally, OA interferes with the integrity and/or function of actomyosin filaments. This results in a dramatic ruffling of the plasma membrane leading to the internalization of large vacuoles, the inhibition of chromosome centrifugal displacement and, consequently, the prevention of polar body extrusion.
Alexandre
H
H
Laboratoire de Cytologie et Embryologie Moléculaires, Université Libre de Bruxelles, Rhode-St-Genèse, Belgium.
Van Cauwenberge
A
A
Tsukitani
Y
Y
Mulnard
J
J
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects*; D004988:Ethers, Cyclic / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D008540:Meiosis / Q000187:drug effects; D000090204:Mesothelin; D051379:Mice; D008870:Microtubules / Q000187:drug effects; D019319:Okadaic Acid; D009865:Oocytes / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004988:Ethers, Cyclic; C000715528:Msln protein, mouse; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D000090204:Mesothelin; D013755:Tetradecanoylphorbol Acetate; D015056:1-Methyl-3-isobutylxanthine