ARF6 Interacts with JIP4 to control a motor switch mechanism regulating endosome traffic in cytokinesis.
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.
Montagnac
Guillaume
G
Institut Curie, Centre de Recherche, Paris, France.
Sibarita
Jean-Baptiste
JB
Loubéry
Sylvain
S
Daviet
Laurent
L
Romao
Maryse
M
Raposo
Graça
G
Chavrier
Philippe
P
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*
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