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The role of calcineurin during exit from meiosis II in Xenopus laevis and The mitotic interplay between the Gwl/Arpp19 module and PP1 in early Xenopus embryos

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The role of calcineurin during exit from meiosis II in Xenopus laevis and The mitotic interplay between the Gwl/Arpp19 module and PP1 in early Xenopus embryos

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HEIM, Andreas, 2018. The role of calcineurin during exit from meiosis II in Xenopus laevis and The mitotic interplay between the Gwl/Arpp19 module and PP1 in early Xenopus embryos [Dissertation]. Konstanz: University of Konstanz

@phdthesis{Heim2018calci-43018, title={The role of calcineurin during exit from meiosis II in Xenopus laevis and The mitotic interplay between the Gwl/Arpp19 module and PP1 in early Xenopus embryos}, year={2018}, author={Heim, Andreas}, address={Konstanz}, school={Universität Konstanz} }

<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dspace="http://digital-repositories.org/ontologies/dspace/0.1.0#" xmlns:foaf="http://xmlns.com/foaf/0.1/" xmlns:void="http://rdfs.org/ns/void#" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/43018"> <dspace:isPartOfCollection rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dspace:hasBitstream rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/43018/3/Heim_2-1ndhey3mjuvyo1.pdf"/> <void:sparqlEndpoint rdf:resource="http://localhost/fuseki/dspace/sparql"/> <dcterms:abstract xml:lang="eng">Faithful meiotic and mitotic cell divisions require the orchestrated activation and inactivation of kinases and phosphatases at defined time points. Today, much is known about the kinases involved in this process and it has been elucidated that cyclin-B/Cdk1 is at the core of a regulatory network that governs entry into meiosis and mitosis. Consequently, exit from meiosis and mitosis requires the inactivation of cyclin-B/Cdk1 by proteolytic degradation of cyclin-B. Reversion of the events that have been initiated by cyclin-B/Cdk1 necessitates that phosphatases act on its meiotic and mitotic substrates. In the work presented here we aimed to investigate the role of the phosphatases calcineurin and PP1 for the correct execution of meiotic and mitotic exit, respectively. It has been reported previously that in Xenopus laevis the increase in cytosolic calcium following fertilization triggers the activation of the phosphatase calcineurin and that this is essential for cyclin-B degradation by the APC/C. However, the exact mechanism remained elusive. Here, we employed extract-based assays to test how calcineurin affects the activation of the APC/C. We found that calcineurin activity is necessary for efficient degradation of the APC/C inhibitor XErp1 during meiotic exit and provide evidence that this depends on interference with the binding of the protective phosphatase PP2A-B56 to XErp1. Furthermore, we show that calcineurin is required to dephosphorylate at least one inhibitory site on the APC/C co-activator Cdc20. Thus, both XErp1 and Cdc20 seem to be substrates of calcineurin that need to be dephosphorylated to fully activate the APC/C during meiotic exit. During entry into mitosis in Xenopus laevis, the main Cdk1-antagonizing phosphatase PP2A-B55 is kept inactive by the Greatwall/Arpp19 module. How this module is subsequently inactivated at mitotic exit to allow PP2A-B55 to act on Cdk1 substrates is not entirely understood. Utilizing cell-free extracts of early Xenopus embryos, we show that the phosphatase PP1 initiates Greatwall inactivation by counteracting its auto-phosphorylation activity. This allows PP2A-B55 to liberate itself from inhibition by Arpp19 and to complete the inactivation of Greatwall. This finding integrates recent reports, which showed that both PP1 and PP2A-B55 are essential for mitotic exit in Xenopus laevis. With this report, we therefore significantly increase the knowledge about the role of the phosphatases calcineurin and PP1 and place them in the regulatory networks that govern exit from meiosis and mitosis.</dcterms:abstract> <dc:creator>Heim, Andreas</dc:creator> <bibo:uri rdf:resource="https://kops.uni-konstanz.de/handle/123456789/43018"/> <dcterms:isPartOf rdf:resource="https://kops.uni-konstanz.de/rdf/resource/123456789/28"/> <dc:contributor>Heim, Andreas</dc:contributor> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2018-08-08T09:53:28Z</dc:date> <dcterms:rights rdf:resource="https://rightsstatements.org/page/InC/1.0/"/> <dc:rights>terms-of-use</dc:rights> <dc:language>eng</dc:language> <dcterms:available rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2018-08-08T09:53:28Z</dcterms:available> <dcterms:title>The role of calcineurin during exit from meiosis II in Xenopus laevis and The mitotic interplay between the Gwl/Arpp19 module and PP1 in early Xenopus embryos</dcterms:title> <foaf:homepage rdf:resource="http://localhost:8080/jspui"/> <dcterms:issued>2018</dcterms:issued> <dcterms:hasPart rdf:resource="https://kops.uni-konstanz.de/bitstream/123456789/43018/3/Heim_2-1ndhey3mjuvyo1.pdf"/> </rdf:Description> </rdf:RDF>

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