title: Interference with kinesin-based anterograde neurofilament axonal transport increases neurofilament-neurofilament bundling.
abstract: Neurofilaments (NFs) associate with each other and with other cytoskeletal elements to form a lattice that supports the mature axon. Phosphorylation contributes to formation of this stationary population of NFs by fostering cation-dependent interactions among NF sidearms. Association of NFs with the stationary phase indirectly competes with NF axonal transport by withdrawing NFs from kinesin-dependent motility along microtubules. We therefore hypothesized that inhibition of anterograde NF transport may increase incorporation into the stationary phase. To test this hypothesis, we treated differentiated NB2a/d1 cells expressing GFP-tagged NF subunits with monastrol, a specific inhibitor of kinesin-5. Monastrol significantly inhibited anterograde axonal transport of NF-H but not NF-M, and increased the incorporation of newly-transported NF subunits into axonal NF bundles. These findings support the notion that NF transport and bundling exert opposing forces on axonal NF dynamics, and that inhibition of anterograde transport of NFs can increase their incorporation into the stationary phase.
authors.affiliation: Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, University of Massachusetts Lowell, Lowell, Massachusetts 01854, USA.
authors.forename: Neethu
authors.initials: N
authors.lastname: Sunil
authors.forename: Sangmook
authors.initials: S
authors.lastname: Lee
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Shea
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000187:drug effects; D007382:Intermediate Filaments / Q000187:drug effects / Q000378:metabolism*; D016547:Kinesins / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D016900:Neurofilament Proteins / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D013871:Thiones / Q000494:pharmacology
chemical_list: D016900:Neurofilament Proteins; D011743:Pyrimidines; D013871:Thiones; C051774:neurofilament protein H; C400223:monastrol; D016547:Kinesins