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The Journal of Neuroscience, October 27, 2004, 24(43):9486-9496; doi:10.1523/JNEUROSCI.1665-04.2004

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Cellular/Molecular
Neurofilament Transport Is Dependent on Actin and Myosin

Cheolwha Jung, Teresa M. Chylinski, Aurea Pimenta, Daniela Ortiz, and Thomas B. Shea

Center for Cellular Neurobiology and Neurodegeneration Research, Departments of Biological Sciences and Biochemistry, University of Massachusetts Lowell, Lowell, Massachusetts 01854

Real-time analyses have revealed that some newly synthesized neurofilament (NF) subunits translocate into and along axonal neurites by moving along the inner plasma membrane surface, suggesting that they may translocate against the submembrane actin cortex. We therefore examined whether or not NF axonal transport was dependent on actin and myosin. Perturbation of filamentous actin in NB2a/d1 cells with cytochalasin B inhibited translocation of subunits into axonal neurites and inhibited bidirectional translocation of NF subunits within neurites. Intravitreal injection of cytochalasin B inhibited NF axonal transport in optic axons in a dose-response manner. NF subunits were coprecipitated from NB2a/d1 cells by an anti-myosin antibody, and myosin colocalized with NFs in immunofluorescent analyses. The myosin light chain kinase inhibitor ML-7 and the myosin ATPase inhibitor 2,3-butanedione-2-monoxime perturbed NF translocation within NB2a/d1 axonal neurites. These findings suggest that some NF subunits may undergo axonal transport via myosin-mediated interactions with the actin cortex.

Key words: actin; axonal transport (axoplasmic transport); cytoskeleton; motor; myosin; neurofilament

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Received May 3, 2004; revised July 16, 2004; accepted July 21, 2004.

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