title: Release from meiotic arrest in ascidian eggs requires the activity of two phosphatases but not CaMKII.
abstract: The fertilising sperm triggers a transient Ca(2+) increase that releases eggs from cell cycle arrest in the vast majority of animal eggs. In vertebrate eggs, Erp1, an APC/C(cdc20) inhibitor, links release from metaphase II arrest with the Ca(2+) transient and its degradation is triggered by the Ca(2+)-induced activation of CaMKII. By contrast, many invertebrate groups have mature eggs that arrest at metaphase I, and these species do not possess the CaMKII target Erp1 in their genomes. As a consequence, it is unknown exactly how cell cycle arrest at metaphase I is achieved and how the fertilisation Ca(2+) transient overcomes the arrest in the vast majority of animal species. Using live-cell imaging with a novel cyclin reporter to study cell cycle arrest and its release in urochordate ascidians, the closest living invertebrate group to the vertebrates, we have identified a new signalling pathway for cell cycle resumption in which CaMKII plays no part. Instead, we find that the Ca(2+)-activated phosphatase calcineurin (CN) is required for egg activation. Moreover, we demonstrate that parthenogenetic activation of metaphase I-arrested eggs by MEK inhibition, independent of a Ca(2+) increase, requires the activity of a second egg phosphatase: PP2A. Furthermore, PP2A activity, together with CN, is required for normal egg activation during fertilisation. As ascidians are a sister group of the vertebrates, we discuss these findings in relation to cell cycle arrest and egg activation in chordates.
authors.affiliation: Institute for Cell and Molecular Biosciences, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Levasseur
authors.forename: Remi
authors.initials: R
authors.lastname: Dumollard
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Chambon
authors.forename: Celine
authors.initials: C
authors.lastname: Hebras
authors.forename: Maureen
authors.initials: M
authors.lastname: Sinclair
authors.forename: Michael
authors.initials: M
authors.lastname: Whitaker
authors.forename: Alex
authors.initials: A
authors.lastname: McDougall
mesh_terms: D064173:Anaphase-Promoting Complex-Cyclosome / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism; D019703:Calcineurin / Q000378:metabolism; D065095:Calcineurin Inhibitors; D002118:Calcium / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D019926:Cyclin B / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005306:Fertilization / Q000187:drug effects; D008322:Mammals / Q000378:metabolism; D008540:Meiosis / Q000187:drug effects; D008677:Metaphase / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D010063:Ovum / Q000166:cytology* / Q000201:enzymology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D054648:Protein Phosphatase 2 / Q000378:metabolism; D051381:Rats; D013379:Substrate Specificity / Q000187:drug effects; D014561:Urochordata / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*
chemical_list: D000952:Antigens, Polyomavirus Transforming; D065095:Calcineurin Inhibitors; D019926:Cyclin B; D064173:Anaphase-Promoting Complex-Cyclosome; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D020928:Mitogen-Activated Protein Kinases; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D002118:Calcium
keywords: CaMKII; Calcineurin; Egg activation; Meiotic arrest; PP2A