title: Expansion of neurofilament medium C terminus increases axonal diameter independent of increases in conduction velocity or myelin thickness.
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.
authors.affiliation: Department of Biological Sciences, University of Missouri, Columbia, Missouri 65211, USA.
authors.forename: Devin M
authors.initials: DM
authors.lastname: Barry
authors.forename: William
authors.initials: W
authors.lastname: Stevenson
authors.forename: Brian G
authors.initials: BG
authors.lastname: Bober
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Wiese
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Dale
authors.forename: Garet S
authors.initials: GS
authors.lastname: Barry
authors.forename: Nathan S
authors.initials: NS
authors.lastname: Byers
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Strope
authors.forename: Rakwoo
authors.initials: R
authors.lastname: Chang
authors.forename: David J
authors.initials: DJ
authors.lastname: Schulz
authors.forename: Sameer
authors.initials: S
authors.lastname: Shah
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Calcutt
authors.forename: Yeshitila
authors.initials: Y
authors.lastname: Gebremichael
authors.forename: Michael L
authors.initials: ML
authors.lastname: Garcia
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure*; D002478:Cells, Cultured; D051379:Mice; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000378:metabolism* / Q000648:ultrastructure*; D009431:Neural Conduction / Q000502:physiology*; D016900:Neurofilament Proteins / Q000378:metabolism* / Q000648:ultrastructure*; D011487:Protein Conformation
chemical_list: D016900:Neurofilament Proteins; C061195:neurofilament protein M