title: ARF6 GTPase protects the post-mitotic midbody from 14-3-3-mediated disintegration.
abstract: In cytokinesis, there is a lengthy interval between cleavage furrow ingression and abscission, during which the midbody microtubule bundle provides both structural support for a narrow intercellular bridge and a platform that orchestrates the biochemical preparations for abscission. It is currently unclear how the midbody structure is stably maintained during this period. Here, we report a novel role for the ADP-ribosylation factor 6 (ARF6) GTPase in the post-mitotic stabilisation of midbody. Centralspindlin kinesin-6/RhoGAP complex, a midbody component critical for both the formation and function of the midbody, assembles in a sharp band at the centre of the structure in a manner antagonised by 14-3-3 protein. We show that ARF6 competes with 14-3-3 for binding to centralspindlin such that midbodies formed by centralspindlin mutants that can bind 14-3-3 but not ARF6 frequently collapse before abscission. These data indicate a novel mechanism for the regulation of midbody dynamics in which ARF6 protects the compacted centralspindlin assembly from dissipation by 14-3-3.
authors.affiliation: The Wellcome Trust/Cancer Research UK Gurdon Institute, University of Cambridge, Cambridge, UK.
authors.forename: Nimesh
authors.initials: N
authors.lastname: Joseph
authors.forename: Andrea
authors.initials: A
authors.lastname: Hutterer
authors.forename: Ina
authors.initials: I
authors.lastname: Poser
authors.forename: Masanori
authors.initials: M
authors.lastname: Mishima
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism*; D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D048749:Cytokinesis; D020558:GTP Phosphohydrolases / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding
chemical_list: D048948:14-3-3 Proteins; D000089982:ADP-Ribosylation Factor 6; D020690:GTPase-Activating Proteins; C085379:rho GTPase-activating protein; D020558:GTP Phosphohydrolases; C526774:KIF6 protein, human; D016547:Kinesins; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human