title: CaM kinase II initiates meiotic spindle depolymerization independently of APC/C activation.
abstract: Altered spindle microtubule dynamics at anaphase onset are the basis for chromosome segregation. In Xenopus laevis egg extracts, increasing free calcium levels and subsequently rising calcium-calmodulin-dependent kinase II (CaMKII) activity promote a release from meiosis II arrest and reentry into anaphase. CaMKII induces the activation of the anaphase-promoting complex/cyclosome (APC/C), which destines securin and cyclin B for degradation to allow chromosome separation and mitotic exit. In this study, we investigated the calcium-dependent signal responsible for microtubule depolymerization at anaphase onset after release from meiotic arrest in Xenopus egg extracts. Using Ran-guanosine triphosphate-mediated microtubule assemblies and quantitative analysis of complete spindles, we demonstrate that CaMKII triggers anaphase microtubule depolymerization. A CaMKII-induced twofold increase in microtubule catastrophe rates can explain reduced microtubule stability. However, calcium or constitutively active CaMKII promotes microtubule destabilization even upon APC/C inhibition and in the presence of high cyclin-dependent kinase 1 activity. Therefore, our data demonstrate that CaMKII turns on parallel pathways to activate the APC/C and to induce microtubule depolymerization at meiotic anaphase onset.
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg, Deutsches Krebsforschungszentrum und Zentrum für Molekulare Biologie Heidelberg Allianz (DKFZ-ZMBH Alliance), 69120 Heidelberg, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Reber
authors.forename: Sabine
authors.initials: S
authors.lastname: Over
authors.forename: Iva
authors.initials: I
authors.lastname: Kronja
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Gruss
mesh_terms: D000705:Anaphase; D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D001704:Biopolymers / Q000378:metabolism*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002457:Cell Extracts; D018385:Centrosome / Q000201:enzymology; D004789:Enzyme Activation; D008540:Meiosis; D008677:Metaphase; D008870:Microtubules / Q000201:enzymology; D010063:Ovum / Q000166:cytology / Q000201:enzymology; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*; D014981:Xenopus / Q000378:metabolism*
chemical_list: D001704:Biopolymers; D002457:Cell Extracts; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D016203:CDC2 Protein Kinase