title: The interaction of Kinesin-1 with its adaptor protein JIP1 can be regulated via proteins binding to the JIP1-PTB domain.
abstract: BACKGROUND
  The regulatory mechanisms of motor protein-dependent intracellular transport are still not fully understood. The kinesin-1-binding protein, JIP1, can function as an adaptor protein that links kinesin-1 and other JIP1-binding "cargo" proteins. However, it is unknown whether these "cargo" proteins influence the JIP1-kinesin-1 binding.
  
  
  RESULTS
  We show here that JIP1-kinesin-1 binding in Neuro2a cells was dependent on conserved amino acid residues in the JIP1-phosphotyrosine binding (PTB) domain, including F687. In addition, mutation of F687 severely affected the neurite tip localization of JIP1. Proteomic analysis revealed another kinesin-1 binding protein, JIP3, as a major JIP1 binding protein. The association between JIP1 and JIP3 was dependent on the F687 residue in JIP1, and this association induced the formation of a stable ternary complex with kinesin-1. On the other hand, the binding of JIP1 and JIP3 was independent of kinesin-1 binding. We also show that other PTB binding proteins can interrupt the formation of the ternary complex.
  
  
  CONCLUSIONS
  The formation of the JIP1-kinesin-1 complex depends on the protein binding-status of the JIP1 PTB domain. This may imply a regulatory mechanism of kinesin-1-dependent intracellular transport.
authors.affiliation: Department of Molecular Biology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Satake
authors.forename: Karin
authors.initials: K
authors.lastname: Otsuki
authors.forename: Yumi
authors.initials: Y
authors.lastname: Banba
authors.forename: Jun
authors.initials: J
authors.lastname: Suenaga
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hirano
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yamanaka
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohno
authors.forename: Syu-ichi
authors.initials: S
authors.lastname: Hirai
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D051379:Mice; D038941:Polypyrimidine Tract-Binding Protein / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D040901:Proteomics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490665:Mapk8ip protein, mouse; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D038941:Polypyrimidine Tract-Binding Protein; D016547:Kinesins