title: Kinetochore components are required for central spindle assembly.
abstract: A critical structure poised to coordinate chromosome segregation with division plane specification is the central spindle that forms between separating chromosomes after anaphase onset. The central spindle acts as a signalling centre that concentrates proteins essential for division plane specification and contractile ring constriction. However, the molecular mechanisms that control the initial stages of central spindle assembly remain elusive. Using Caenorhabditis elegans zygotes, we found that the microtubule-bundling protein SPD-1(PRC1) and the motor ZEN-4(MKLP-1) are required for proper central spindle structure during its elongation. In contrast, we found that the kinetochore controls the initiation of central spindle assembly. Specifically, central spindle microtubule assembly is dependent on kinetochore recruitment of the scaffold protein KNL-1, as well as downstream partners BUB-1, HCP-1/2(CENP-F) and CLS-2(CLASP); and is negatively regulated by kinetochore-associated protein phosphatase 1 activity. This in turn promotes central spindle localization of CLS-2(CLASP) and initial central spindle microtubule assembly through its microtubule polymerase activity. Together, our results reveal an unexpected role for a conserved kinetochore protein network in coupling two critical events of cell division: chromosome segregation and cytokinesis.
authors: Institut Jacques Monod, CNRS, UMR 7592, University Paris Diderot, Sorbonne Paris Cité F-75205 Paris, France.
authors: Gilliane
authors: G
authors: Maton
authors: Institut Jacques Monod, CNRS, UMR 7592, University Paris Diderot, Sorbonne Paris Cité F-75205 Paris, France.
authors: Frances
authors: F
authors: Edwards
authors: Institut Jacques Monod, CNRS, UMR 7592, University Paris Diderot, Sorbonne Paris Cité F-75205 Paris, France.
authors: Benjamin
authors: B
authors: Lacroix
authors: Institut Jacques Monod, CNRS, UMR 7592, University Paris Diderot, Sorbonne Paris Cité F-75205 Paris, France.
authors: Marine
authors: M
authors: Stefanutti
authors: Institut Jacques Monod, CNRS, UMR 7592, University Paris Diderot, Sorbonne Paris Cité F-75205 Paris, France.
authors: Kimberley
authors: K
authors: Laband
authors: Institut Jacques Monod, CNRS, UMR 7592, University Paris Diderot, Sorbonne Paris Cité F-75205 Paris, France.
authors: Tiffany
authors: T
authors: Lieury
authors: Ludwig Institute for Cancer Research/Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093, USA.
authors: Taekyung
authors: T
authors: Kim
authors: Université Montpellier, CRBM, CNRS UMR 5237, 34293 Montpellier, France.
authors: Julien
authors: J
authors: Espeut
authors: Columbia University, Department of Pathology and Cell Biology, New York, New York 10033, USA.
authors: Julie C
authors: JC
authors: Canman
authors: Institut Jacques Monod, CNRS, UMR 7592, University Paris Diderot, Sorbonne Paris Cité F-75205 Paris, France.
authors: Julien
authors: J
authors: Dumont
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation; D048749:Cytokinesis; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: C575826:CLS-2 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002868:Chromosomal Proteins, Non-Histone; C400273:HCP-2 protein, C elegans; C478660:KNL-1 protein, C elegans; D008869:Microtubule-Associated Proteins; C495574:SPD-1 protein, C elegans; C114455:ZEN-4 protein, C elegans; C400272:hcp-1 protein, C elegans; D017346:Protein Serine-Threonine Kinases; C588208:bub-1 protein, C elegans; D016547:Kinesins