4.4 Article

Tight Functional Coupling of Kinesin-1A and Dynein Motors in the Bidirectional Transport of Neurofilaments

Journal

MOLECULAR BIOLOGY OF THE CELL
Volume 20, Issue 23, Pages 4997-5006

Publisher

AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E09-04-0304

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Funding

  1. National Institutes of Health [R01-NS38526, P30-NS045758]
  2. Japan Ministry of Education, Culture, Sports, Science and Technology
  3. Hayashi Memorial Foundation for Female Natural Scientists
  4. NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS038526, P30NS045758] Funding Source: NIH RePORTER

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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.

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