title: Coordinated regulation of the ESCRT-III component CHMP4C by the chromosomal passenger complex and centralspindlin during cytokinesis.
abstract: The chromosomal passenger complex (CPC)-composed of Aurora B kinase, Borealin, Survivin and INCENP-surveys the fidelity of genome segregation throughout cell division. The CPC has been proposed to prevent polyploidy by controlling the final separation (known as abscission) of the two daughter cells via regulation of the ESCRT-III CHMP4C component. The molecular details are, however, still unclear. Using atomic force microscopy, we show that CHMP4C binds to and remodels membranes in vitro Borealin prevents the association of CHMP4C with membranes, whereas Aurora B interferes with CHMP4C's membrane remodelling activity. Moreover, we show that CHMP4C phosphorylation is not required for its assembly into spiral filaments at the abscission site and that two distinctly localized pools of phosphorylated CHMP4C exist during cytokinesis. We also characterized the CHMP4C interactome in telophase cells and show that the centralspindlin complex associates preferentially with unphosphorylated CHMP4C in cytokinesis. Our findings indicate that gradual dephosphorylation of CHMP4C triggers a 'relay' mechanism between the CPC and centralspindlin that regulates the timely distribution and activation of CHMP4C for the execution of abscission.
authors: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK lc284@cam.ac.uk.
authors: Luisa
authors: L
authors: Capalbo
authors: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.
authors: Ioanna
authors: I
authors: Mela
authors: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Mayfield Road, Edinburgh EH9 3JR, UK.
authors: Maria Alba
authors: MA
authors: Abad
authors: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Mayfield Road, Edinburgh EH9 3JR, UK.
authors: A Arockia
authors: AA
authors: Jeyaprakash
authors: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.
authors: J Michael
authors: JM
authors: Edwardson
authors: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK ppd21@cam.ac.uk.
authors: Pier Paolo
authors: 0000-0002-4773-6950
authors: PP
authors: D'Avino
mesh_terms: D064107:Aurora Kinase B / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D048749:Cytokinesis; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018625:Microscopy, Atomic Force; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D060066:Protein Interaction Maps; D008941:Spindle Apparatus / Q000378:metabolism*; D013692:Telophase
chemical_list: C490157:CDCA8 protein, human; C541008:CHMP4C protein, human; D018797:Cell Cycle Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D008869:Microtubule-Associated Proteins; C576921:AURKB protein, human; D064107:Aurora Kinase B
keywords: Aurora B; cell division; centralspindlin; cytokinesis; membrane remodelling; midbody