title: Kinesin-1 regulates microtubule dynamics via a c-Jun N-terminal kinase-dependent mechanism.
abstract: In the kinesin family, all the molecular motors that have been implicated in the regulation of microtubule dynamics have been shown to stimulate microtubule depolymerization. Here, we report that kinesin-1 (also known as conventional kinesin or KIF5B) stimulates microtubule elongation and rescues. We show that microtubule-associated kinesin-1 carries the c-Jun N-terminal kinase (JNK) to allow its activation and that microtubule elongation requires JNK activity throughout the microtubule life cycle. We also show that kinesin-1 and JNK promoted microtubule rescues to similar extents. Stimulation of microtubule rescues by the kinesin-1/JNK pathway could not be accounted for by the rescue factor CLIP-170. Indeed only a dual inhibition of kinesin-1/JNK and CLIP-170 completely blocked rescues and led to extensive microtubule loss. We propose that the kinesin-1/JNK signaling pathway is a major regulator of microtubule dynamics in living cells and that it is required with the rescue factor CLIP-170 to allow cells to build their interphase microtubule network.
authors.affiliation: Faculté de Pharmacie, Université Paris-Sud 11, JE2493, IFR141, 92296 Châtenay-Malabry Cedex, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Daire
authors.forename: Julien
authors.initials: J
authors.lastname: Giustiniani
authors.forename: Ingrid
authors.initials: I
authors.lastname: Leroy-Gori
authors.forename: Mélanie
authors.initials: M
authors.lastname: Quesnoit
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Drevensek
authors.forename: Ariane
authors.initials: A
authors.lastname: Dimitrov
authors.forename: Franck
authors.initials: F
authors.lastname: Perez
authors.forename: Christian
authors.initials: C
authors.lastname: Poüs
mesh_terms: D015153:Blotting, Western; D005455:Fluorescent Antibody Technique; D005799:Genes, Dominant; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D016547:Kinesins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D008845:Microinjections; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D008941:Spindle Apparatus
chemical_list: D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C076744:cytoplasmic linker protein 170; D048031:JNK Mitogen-Activated Protein Kinases; D016547:Kinesins