Expansion of neurofilament medium C terminus increases axonal diameter
independent of increases in conduction velocity or myelin thickness.
Authors Barry DM, Stevenson W, Bober BG, Wiese PJ, Dale JM, Barry GS, Byers NS, Strope
JD, Chang R, Schulz DJ, Shah S, Calcutt NA, Gebremichael Y, Garcia ML
Submitted By Nigel Calcutt on 1/30/2013
Status Published
Journal The Journal of neuroscience : the official journal of the Society for Neuroscience
Year 2012
Date Published 5/2/2012
Volume : Pages 32 : 6209 - 6219
PubMed Reference 22553027
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 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.

Investigators with authorship
Nigel CalcuttUniversity of California San Diego