Sequential Cyk-4 binding to ECT2 and FIP3 regulates cleavage furrow ingression and abscission during cytokinesis

EMBO J. 2008 Jul 9;27(13):1791-803. doi: 10.1038/emboj.2008.112. Epub 2008 May 29.

Abstract

Cytokinesis is a highly regulated and dynamic event that involves the reorganization of the cytoskeleton and membrane compartments. Recently, FIP3 has been implicated in targeting of recycling endosomes to the mid-body of dividing cells and is found required for abscission. Here, we demonstrate that the centralspindlin component Cyk-4 is a FIP3-binding protein. Furthermore, we show that FIP3 binds to Cyk-4 at late telophase and that centralspindlin may be required for FIP3 recruitment to the mid-body. We have mapped the FIP3-binding region on Cyk-4 and show that it overlaps with the ECT2-binding domain. Finally, we demonstrate that FIP3 and ECT2 form mutually exclusive complexes with Cyk-4 and that dissociation of ECT2 from the mid-body at late telophase may be required for the recruitment of FIP3 and recycling endosomes to the cleavage furrow. Thus, we propose that centralspindlin complex not only regulates acto-myosin ring contraction but also endocytic vesicle transport to the cleavage furrow and it does so through sequential interactions with ECT2 and FIP3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factor 6
  • ADP-Ribosylation Factors / metabolism
  • Actins / metabolism
  • Cell Division
  • Cytokinesis*
  • Endosomes / metabolism*
  • GTPase-Activating Proteins / metabolism*
  • HeLa Cells
  • Humans
  • I-kappa B Kinase / metabolism*
  • Proto-Oncogene Proteins / metabolism*
  • rab GTP-Binding Proteins / metabolism

Substances

  • ADP-Ribosylation Factor 6
  • Actins
  • ECT2 protein, human
  • GTPase-Activating Proteins
  • IKBKG protein, human
  • Proto-Oncogene Proteins
  • mgcRacGAP
  • I-kappa B Kinase
  • rab11 protein
  • ADP-Ribosylation Factors
  • rab GTP-Binding Proteins