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 language | English |
---|---|
Pages (from-to) | 6209-6219 |
Number of pages | 11 |
Journal | Journal of Neuroscience |
Volume | 32 |
Issue number | 18 |
DOIs | |
State | Published - 2 May 2012 |