NF-M is an essential target for the myelin-directed "outside-in" signaling cascade that mediates radial axonal growth

Michael L. Garcia, Christian S. Lobsiger, Sameer B. Shah, Tom J. Deerinck, John Crum, Darren Young, Christopher M. Ward, Thomas Owen Crawford, Takahiro Gotow, Yasuo Uchiyama, Mark H. Ellisman, Nigel A. Calcutt, Don W. Cleveland

Research output: Contribution to journalArticle

Abstract

Neurofilaments are essential for acquisition of normal axonal calibers. Several lines of evidence have suggested that neurofilament-dependent structuring of axoplasm arises through an "outside-in" signaling cascade originating from myelinating cells. Implicated as targets in this cascade are the highly phosphorylated KSP domains of neurofilament subunits NF-H and NF-M. These are nearly stoichiometrically phosphorylated in myelinated internodes where radial axonal growth takes place, but not in the smaller, unmyelinated nodes. Gene replacement has now been used to produce mice expressing normal levels of the three neurofilament subunits, but which are deleted in the known phosphorylation sites within either NF-M or within both NF-M and NF-H. This has revealed that the tail domain of NF-M, with seven KSP motifs, is an essential target for the myelination-dependent outside-in signaling cascade that determines axonal caliber and conduction velocity of motor axons.

Original languageEnglish (US)
Pages (from-to)1011-1020
Number of pages10
JournalJournal of Cell Biology
Volume163
Issue number5
DOIs
StatePublished - Dec 8 2003

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Keywords

  • Axon caliber
  • Myelin
  • Neurofilaments
  • Phosphorylation
  • Radial growth

ASJC Scopus subject areas

  • Cell Biology

Cite this

Garcia, M. L., Lobsiger, C. S., Shah, S. B., Deerinck, T. J., Crum, J., Young, D., Ward, C. M., Crawford, T. O., Gotow, T., Uchiyama, Y., Ellisman, M. H., Calcutt, N. A., & Cleveland, D. W. (2003). NF-M is an essential target for the myelin-directed "outside-in" signaling cascade that mediates radial axonal growth. Journal of Cell Biology, 163(5), 1011-1020. https://doi.org/10.1083/jcb.200308159