1. NF-M is an essential target for the myelin-directed "outside-in" signaling cascade that mediates radial axonal growth.
- Author
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Garcia ML, Lobsiger CS, Shah SB, Deerinck TJ, Crum J, Young D, Ward CM, Crawford TO, Gotow T, Uchiyama Y, Ellisman MH, Calcutt NA, and Cleveland DW
- Subjects
- Action Potentials physiology, Amino Acid Motifs, Animals, Axons pathology, Mice, Mice, Transgenic, Models, Biological, Motor Activity, Nerve Fibers, Myelinated metabolism, Nerve Fibers, Myelinated pathology, Neurofilament Proteins genetics, Phosphorylation, Protein Structure, Tertiary, Protein Subunits genetics, Protein Subunits metabolism, Axons metabolism, Myelin Sheath metabolism, Neurofilament Proteins metabolism, Signal Transduction physiology
- 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.
- Published
- 2003
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