Tight functional coupling of kinesin-1A and dynein motors in the bidirectional transport of neurofilaments.
We have tested the hypothesis that kinesin-1A (formerly KIF5A) is an anterograde motor for axonal neurofilaments. In cultured sympathetic neurons from kinesin-1A knockout mice, we observed a 75% reduction in the frequency of both anterograde and retrograde neurofilament movement. This transport defect could be rescued by kinesin-1A, and with successively decreasing efficacy by kinesin-1B and kinesin-1C. In wild-type neurons, headless mutants of kinesin-1A and kinesin-1C inhibited both anterograde and retrograde movement in a dominant-negative manner. Because dynein is thought to be the retrograde motor for axonal neurofilaments, we investigated the effect of dynein inhibition on anterograde and retrograde neurofilament transport. Disruption of dynein function by using RNA interference, dominant-negative approaches, or a function-blocking antibody also inhibited both anterograde and retrograde neurofilament movement. These data suggest that kinesin-1A is the principal but not exclusive anterograde motor for neurofilaments in these neurons, that there may be some functional redundancy among the kinesin-1 isoforms with respect to neurofilament transport, and that the activities of the anterograde and retrograde neurofilament motors are tightly coordinated.
Uchida
Atsuko
A
Center for Molecular Neurobiology and Department of Neuroscience, The Ohio State University, Columbus, OH 43210, USA.
Alami
Nael H
NH
Brown
Anthony
A
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D000072159:Dynactin Complex; D004398:Dyneins / Q000235:genetics / Q000378:metabolism*; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D016900:Neurofilament Proteins / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D034622:RNA Interference; D013564:Sympathetic Nervous System / Q000166:cytology
D000072159:Dynactin Complex; C507512:Kif5A protein, mouse; D008869:Microtubule-Associated Proteins; D016900:Neurofilament Proteins; D020033:Protein Isoforms; D004398:Dyneins; D016547:Kinesins