ARF6 Interacts With JIP4 to Control a Motor Switch Mechanism Regulating Endosome Traffic in Cytokinesis

Curr Biol. 2009 Feb 10;19(3):184-95. doi: 10.1016/j.cub.2008.12.043.

Abstract

Background: Recent work has highlighted the importance of the recycling of endocytic membranes to the intercellular bridge for completion of cytokinesis in animal cells. ADP-ribosylation factor 6 (ARF6), which localizes to the plasma membrane and endosomal compartments, regulates endocytic recycling to the bridge during cytokinesis and is required for abscission.

Results: Here, we report that the JNK-interacting proteins JIP3 and JIP4, two highly related scaffolding proteins for JNK signaling modules, also acting as binding partners of kinesin-1 and dynactin complex, can function as downstream effectors of ARF6. In vitro, binding of GTP-ARF6 to the second leucine zipper domain of JIP3 and JIP4 interferes with JIPs' association with kinesin-1, whereas it favors JIPs' interaction with the dynactin complex. With protein silencing by small interfering RNA and dominant inhibition approaches, we show that ARF6, JIP4, kinesin-1, and the dynactin complex control the trafficking of recycling endosomes in and out of the intercellular bridge and are necessary for abscission.

Conclusion: Our findings reveal a novel function for ARF6 as a regulatory switch for motor proteins of opposing direction that controls trafficking of endocytic vesicles within the intercellular bridge in a mechanism required for abscission.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factors / metabolism*
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Biological Transport / physiology
  • Cytokinesis / genetics
  • Cytokinesis / physiology*
  • Dynactin Complex
  • Endosomes / metabolism*
  • Fluorescence Recovery After Photobleaching
  • Fluorescent Antibody Technique, Indirect
  • HeLa Cells
  • Humans
  • Kinesin / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Dynactin Complex
  • MAPK8IP3 protein, human
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • SPAG9 protein, human
  • Kinesin
  • ADP-Ribosylation Factors
  • ADP-ribosylation factor 6