title: Aurora B kinase promotes cytokinesis by inducing centralspindlin oligomers that associate with the plasma membrane.
abstract: In metazoans, cytokinesis is triggered by activation of the GTPase RhoA at the equatorial plasma membrane. ECT-2, the guanine nucleotide exchange factor (GEF) required for RhoA activation, is activated by the centralspindlin complex that concentrates on spindle midzone microtubules. However, these microtubules and the plasma membrane are not generally in apposition, and thus the mechanism by which RhoA is activated at the cell equator remains unknown. Here we report that a regulated pool of membrane-bound, oligomeric centralspindlin stimulates RhoA activation. The membrane-binding C1 domain of CYK-4, a centralspindlin component, promotes furrow initiation in C. elegans embryos and human cells. Membrane localization of centralspindlin oligomers is globally inhibited by PAR-5/14-3-3. This activity is antagonized by the chromosome passenger complex (CPC), resulting in RhoA activation at the nascent cleavage site. Therefore, CPC-directed centralspindlin oligomerization during anaphase induces contractile ring assembly at the membrane.
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Angika
authors.initials: A
authors.lastname: Basant
authors.affiliation: Cell Division and Aneuploidy Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, UK.
authors.forename: Sergey
authors.initials: S
authors.lastname: Lekomtsev
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Yu Chung
authors.initials: YC
authors.lastname: Tse
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Donglei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA.
authors.forename: Katrina M
authors.initials: KM
authors.lastname: Longhini
authors.affiliation: Cell Division and Aneuploidy Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Petronczki
authors.affiliation: Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637, USA. Electronic address: mglotzer@uchicago.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Glotzer
mesh_terms: D000818:Animals; D064107:Aurora Kinase B / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000196:embryology*; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D048749:Cytokinesis / Q000235:genetics*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering; D008941:Spindle Apparatus / Q000235:genetics; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: C513388:CYK-4 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C507872:Ect-2 protein, C elegans; D020662:Guanine Nucleotide Exchange Factors; C092935:KIF23 protein, human; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; C106207:par-5 protein, C elegans; D064107:Aurora Kinase B; C491506:air-2 protein, C elegans; D020742:rhoA GTP-Binding Protein