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. |