ARF6 GTPase protects the post-mitotic midbody from 14-3-3-mediated disintegration

EMBO J. 2012 May 30;31(11):2604-14. doi: 10.1038/emboj.2012.139. Epub 2012 May 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / metabolism*
  • ADP-Ribosylation Factors / metabolism*
  • Cytokinesis
  • GTP Phosphohydrolases / metabolism
  • GTPase-Activating Proteins / metabolism
  • HeLa Cells
  • Humans
  • Kinesin / genetics
  • Kinesin / metabolism
  • Mutation
  • Protein Binding

Substances

  • 14-3-3 Proteins
  • GTPase-Activating Proteins
  • rho GTPase-activating protein
  • GTP Phosphohydrolases
  • KIF6 protein, human
  • Kinesin
  • ADP-Ribosylation Factors
  • ADP-ribosylation factor 6