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Myosin Va binding to neurofilaments is essential for correct myosin Va distribution and transport and neurofilament density.

The Journal of cell biology | 2002

The identification of molecular motors that modulate the neuronal cytoskeleton has been elusive. Here, we show that a molecular motor protein, myosin Va, is present in high proportions in the cytoskeleton of mouse CNS and peripheral nerves. Immunoelectron microscopy, coimmunoprecipitation, and blot overlay analyses demonstrate that myosin Va in axons associates with neurofilaments, and that the NF-L subunit is its major ligand. A physiological association is indicated by observations that the level of myosin Va is reduced in axons of NF-L-null mice lacking neurofilaments and increased in mice overexpressing NF-L, but unchanged in NF-H-null mice. In vivo pulse-labeled myosin Va advances along axons at slow transport rates overlapping with those of neurofilament proteins and actin, both of which coimmunoprecipitate with myosin Va. Eliminating neurofilaments from mice selectively accelerates myosin Va translocation and redistributes myosin Va to the actin-rich subaxolemma and membranous organelles. Finally, peripheral axons of dilute-lethal mice, lacking functional myosin Va, display selectively increased neurofilament number and levels of neurofilament proteins without altering axon caliber. These results identify myosin Va as a neurofilament-associated protein, and show that this association is essential to establish the normal distribution, axonal transport, and content of myosin Va, and the proper numbers of neurofilaments in axons.

Pubmed ID: 12403814 RIS Download

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Associated grants

  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK 19525
  • Agency: NIA NIH HHS, United States
    Id: R01 AG005604
  • Agency: NIA NIH HHS, United States
    Id: AG 05604
  • Agency: NIA NIH HHS, United States
    Id: 2T32 AG 00222
  • Agency: NIA NIH HHS, United States
    Id: T32 AG000222
  • Agency: NIA NIH HHS, United States
    Id: R37 AG005604
  • Agency: NIDDK NIH HHS, United States
    Id: P30 DK019525

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C57BL/6J (tool)

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Mus musculus with name C57BL/6J from IMSR.

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