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

Devin M. Barry, William Stevenson, Brian G. Bober, Peter J. Wiese, Jeffrey M. Dale, Garet S. Barry, Nathan S. Byers, Jonathan D. Strope, Rakwoo Chang, David J. Schulz, Sameer Shah, Nigel A. Calcutt, Yeshitila Gebremichael, Michael L. Garcia

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40 Scopus citations

Abstract

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 neuro filament 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 neuro filament subunit stoichiometry. Computational modeling predicted that an expanded NF-M C terminus extended farther from the neuro filament core independent of lysine-serine-proline (KSP) phosphorylation. However, expansion of NF-MC 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 my elinto compensate for larger axonal diameters suggested a lack of plasticity during the processes of myelination and radial axonal growth.

Original languageEnglish
Pages (from-to)6209-6219
Number of pages11
JournalJournal of Neuroscience
Volume32
Issue number18
DOIs
StatePublished - 2 May 2012

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