title: JSAP1 and JLP are required for ARF6 localization to the midbody in cytokinesis.
abstract: The ADP-ribosylation factor 6 (ARF6) GTPase is important in cytokinesis and localizes to the midbody. However, the mechanism and regulation of ARF6's recruitment to the midbody are largely unknown. Here, we investigated the functions of two binding partners of active ARF6, c-Jun NH2 -terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1) and JNK-associated leucine zipper protein (JLP), by gene knockout and rescue experiments in mouse embryonic fibroblasts. Depleting both JSAP1 and JLP impaired ARF6's localization to the midbody and delayed cytokinesis. These defects were almost completely rescued by wild-type JSAP1 or JLP, but not by JSAP1 or JLP mutants that were unable to interact with active ARF6 or with the kinesin heavy chain (KHC) of kinesin-1. In transfected cells, a constitutively active form of ARF6 associated with KHC only when co-expressed with wild-type JSAP1 or JLP and not with a JSAP1 or JLP mutant. These findings suggest that JSAP1 and JLP, which might be paralogous to each other, are critical and functionally redundant in cytokinesis and control ARF6 localization to the midbody by forming a tripartite complex of JSAP1/JLP, active ARF6, and kinesin-1.
authors.affiliation: Division of Molecular Cell Signaling, Cancer Research Institute, Kanazawa University, Kanazawa, 920-1192, Japan.
authors.forename: Baljinnyam
authors.initials: B
authors.lastname: Tuvshintugs
authors.forename: Tokiharu
authors.initials: T
authors.lastname: Sato
authors.forename: Radnaa
authors.initials: R
authors.lastname: Enkhtuya
authors.forename: Katsumi
authors.initials: K
authors.lastname: Yamashita
authors.forename: Katsuji
authors.initials: K
authors.lastname: Yoshioka
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D048749:Cytokinesis; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization
chemical_list: D000089982:ADP-Ribosylation Factor 6; D048868:Adaptor Proteins, Signal Transducing; C403619:Mapk8ip3 protein, mouse; D009419:Nerve Tissue Proteins; C468928:Spag9 protein, mouse; D016547:Kinesins; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human; C000715727:Arf6 protein, mouse