Expansion of NF-M carboxy terminus increases axonal diameter independent of increases in conduction velocity or myelin thickness

Autor: Barry, Devin M., Stevenson, William, Bober, Brian G., Wiese, Peter J., Dale, Jeffrey M., Barry, Garet S., Byers, Nathan S., Strope, Jonathan D., Chang, Rakwoo, Schulz, David J., Shah, Sameer, Calcutt, Nigel A., Gebremichael, Yeshitila, Garcia, Michael L.
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Popis: 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 region of neurofilament medium (NF-M). Molecular phylogenetic analysis in mammals suggested that expanded NF-M C-termini correlated with larger diameter axons. We utilized 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.
Databáze: OpenAIRE