title: ARF6 Interacts with JIP4 to control a motor switch mechanism regulating endosome traffic in cytokinesis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institut Curie, Centre de Recherche, Paris, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Montagnac
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Sibarita
authors.forename: Sylvain
authors.initials: S
authors.lastname: Loubéry
authors.forename: Laurent
authors.initials: L
authors.lastname: Daviet
authors.forename: Maryse
authors.initials: M
authors.lastname: Romao
authors.forename: Graça
authors.initials: G
authors.lastname: Raposo
authors.forename: Philippe
authors.initials: P
authors.lastname: Chavrier
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D048749:Cytokinesis / Q000235:genetics / Q000502:physiology*; D000072159:Dynactin Complex; D011992:Endosomes / Q000378:metabolism*; D036681:Fluorescence Recovery After Photobleaching; D019084:Fluorescent Antibody Technique, Indirect; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*
chemical_list: D000089982:ADP-Ribosylation Factor 6; D048868:Adaptor Proteins, Signal Transducing; D000072159:Dynactin Complex; C485750:MAPK8IP3 protein, human; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; C111047:SPAG9 protein, human; D016547:Kinesins; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human