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Publication : Expansion of neurofilament medium C terminus increases axonal diameter independent of increases in conduction velocity or myelin thickness.

First Author  Barry DM Year  2012
Journal  J Neurosci Volume  32
Issue  18 Pages  6209-19
PubMed ID  22553027 Mgi Jnum  J:184861
Mgi Id  MGI:5426480 Doi  10.1523/JNEUROSCI.0647-12.2012
Citation  Barry DM, et al. (2012) Expansion of neurofilament medium C terminus increases axonal diameter independent of increases in conduction velocity or myelin thickness. J Neurosci 32(18):6209-19
abstractText  Maturation of the peripheral nervous system requires specification of axonal diameter, which, in turn, has a significant influence on nerve conduction velocity. Radial axonal growth initiates with myelination, and is dependent upon the C terminus of neurofilament medium (NF-M). Molecular phylogenetic analysis in mammals suggested that expanded NF-M C termini correlated with larger-diameter axons. We used gene targeting and computational modeling to test this new hypothesis. Increasing the length of NF-M C terminus in mice increased diameter of motor axons without altering neurofilament subunit stoichiometry. Computational modeling predicted that an expanded NF-M C terminus extended farther from the neurofilament core independent of lysine-serine-proline (KSP) phosphorylation. However, expansion of NF-M C terminus did not affect the distance between adjacent neurofilaments. Increased axonal diameter did not increase conduction velocity, possibly due to a failure to increase myelin thickness by the same proportion. Failure of myelin to compensate for larger axonal diameters suggested a lack of plasticity during the processes of myelination and radial axonal growth.
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