Coordinated regulation of the ESCRT-III component CHMP4C by the chromosomal passenger complex and centralspindlin during cytokinesis.
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.
['Capalbo|Luisa|L|', 'Mela|Ioanna|I|', 'Abad|Maria Alba|MA|', 'Jeyaprakash|A Arockia|AA|', 'Edwardson|J Michael|JM|', "D'Avino|Pier Paolo|PP|0000-0002-4773-6950"]
D064107:Aurora Kinase B D018797:Cell Cycle Proteins D002462:Cell Membrane D048749:Cytokinesis D056827:Endosomal Sorting Complexes Required for Transport D006367:HeLa Cells D006801:Humans D018625:Microscopy, Atomic Force D008869:Microtubule-Associated Proteins D010766:Phosphorylation D011485:Protein Binding D060066:Protein Interaction Maps D008941:Spindle Apparatus D013692:Telophase
centralspindlin cytokinesis Aurora B cell division membrane remodelling midbody