title: The chromosomal passenger complex and centralspindlin independently contribute to contractile ring assembly.
abstract: The chromosomal passenger complex (CPC) and centralspindlin are conserved cytokinesis regulators that localize to the spindle midzone, which forms between the separating chromosomes. Previous work placed the CPC and centralspindlin in a linear pathway that governs midzone formation. Using Caenorhabditis elegans embryos, we test whether there is a similar linear relationship between centralspindlin and the CPC in contractile ring constriction during cytokinesis. We show that simultaneous inhibition of the CPC kinase Aurora B(AIR-2) and the centralspindlin component MKLP1(ZEN-4) causes an additive constriction defect. Consistent with distinct roles for the proteins, inhibition of filamentous septin guanosine triphosphatases alleviates constriction defects in Aurora B(AIR-2)-inhibited embryos, whereas inhibition of Rac does so in MKLP1(ZEN-4)-inhibited embryos. Centralspindlin and the CPC are not required to enrich ring proteins at the cell equator but instead regulate formation of a compact mature ring. Therefore, in contrast to the linear midzone assembly pathway, centralspindlin and the CPC make independent contributions to control transformation of the sheet-like equatorial band into a ribbon-like contractile ring at the furrow tip.
authors.affiliation: Department of Cellular and Molecular Medicine, Biomedical Sciences Graduate Program, Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, CA 92093, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Lewellyn
authors.forename: Ana
authors.initials: A
authors.lastname: Carvalho
authors.forename: Arshad
authors.initials: A
authors.lastname: Desai
authors.forename: Amy S
authors.initials: AS
authors.lastname: Maddox
authors.forename: Karen
authors.initials: K
authors.lastname: Oegema
mesh_terms: D000818:Animals; D064107:Aurora Kinase B; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D002875:Chromosomes / Q000378:metabolism* / Q000648:ultrastructure; D048749:Cytokinesis; D005838:Genotype; D016547:Kinesins / Q000037:antagonists & inhibitors / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C490517:MKLP1 protein, C elegans; D008869:Microtubule-Associated Proteins; D010750:Phosphoproteins; C114455:ZEN-4 protein, C elegans; C104434:spindlin; D064107:Aurora Kinase B; D017346:Protein Serine-Threonine Kinases; C491506:air-2 protein, C elegans; D016547:Kinesins