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Neurofilament heavy chain side arm phosphorylation regulates axonal transport of neurofilaments
Open accessAbstract
Neurofilaments possess side arms that comprise the carboxy-terminal domains of neurofilament middle and heavy chains (NFM and NFH); that of NFH is heavily phosphorylated in axons. Here, we demonstrate that phosphorylation of NFH side arms is a mechanism for regulating transport of neurofilaments through axons. Mutants in which known NFH phosphorylation sites were mutated to preclude phosphorylation or mimic permanent phosphorylation display altered rates of transport in a bulk transport assay. Similarly, application of roscovitine, an inhibitor of the NFH side arm kinase Cdk5/p35, accelerates neurofilament transport. Analyses of neurofilament movement in transfected living neurons demonstrated that a mutant mimicking permanent phosphorylation spent a higher proportion of time pausing than one that could not be phosphorylated. Thus, phosphorylation of NFH slows neurofilament transport, and this is due to increased pausing in neurofilament movement.
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Eidenmüller, J., Fath, T., Hellwig, A., Reed, J., Sontag, E., & Brandt, R. (2000) · Biochemistry · doi:10.1021/bi001290z · Cited by 117
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Axonal transport deficits and neurodegenerative diseases
Millecamps, S., & Julien, J.-P. (2013) · Nature Reviews Neuroscience · doi:10.1038/nrn3380 · Cited by 755
Neurofilaments and Neurofilament Proteins in Health and Disease
Yuan, A., Rao, M. V., Veeranna, & Nixon, R. A. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a018309 · Cited by 731
Molecular pathways of motor neuron injury in amyotrophic lateral sclerosis
Ferraiuolo, L., Kirby, J., Grierson, A. J., Sendtner, M., & Shaw, P. J. (2011) · Nature Reviews Neurology · doi:10.1038/nrneurol.2011.152 · Cited by 615
Self-citationYuan, A., Rao, M. V., Veeranna, & Nixon, R. A. (2012) · Journal of Cell Science · doi:10.1242/jcs.104729 · Cited by 402
Metadata
- Authors
- Ackerley, S., Thornhill, P., Grierson, A. J., Brownlees, J., Anderton, B. H., Leigh, P. N., Shaw, C. E., & Miller, C. C. J.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2003-05-12
- Volume
- 161
- Issue
- 3
- Pages
- 489-495
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2056274705
- Cited by
- 194
- References
- 1
- FWCI
- 5.81
- Type
- journal article
- Language
- en
- Open access
- green
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- Ackerley, S., Thornhill, P., Grierson, A. J., Brownlees, J., Anderton, B. H., Leigh, P. N., Shaw, C. E., & Miller, C. C. J. (2003). Neurofilament heavy chain side arm phosphorylation regulates axonal transport of neurofilaments. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200303138
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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