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

Guillaume Montagnac, Jean-Baptiste Sibarita, Sylvain Loubéry, Laurent Daviet, Maryse Romao, Graça Raposo, Philippe Chavrier
Current Biology. 2009-02-01; 19(3): 184-195
DOI: 10.1016/j.cub.2008.12.043

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

ARF6 Interacts with JIP4 to control a motor switch mechanism regulating endosome
traffic in cytokinesis.

Montagnac G(1), Sibarita JB, Loubéry S, Daviet L, Romao M, Raposo G, Chavrier P.

Author information:
(1)Institut Curie, Centre de Recherche, Paris, France.

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.