Kinesin-1 regulates microtubule dynamics via a c-Jun N-terminal kinase-dependent mechanism.
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.
Daire
Vanessa
V
Faculté de Pharmacie, Université Paris-Sud 11, JE2493, IFR141, 92296 Châtenay-Malabry Cedex, France.
Giustiniani
Julien
J
Leroy-Gori
Ingrid
I
Quesnoit
Mélanie
M
Drevensek
Stéphanie
S
Dimitrov
Ariane
A
Perez
Franck
F
Poüs
Christian
C
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
D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C076744:cytoplasmic linker protein 170; D048031:JNK Mitogen-Activated Protein Kinases; D016547:Kinesins