Molecular mechanisms of radial axonal growth : insights from analysis of neurofilament gene-targeted mice

Maturation of the peripheral nervous system requires establishment of axonal diameter which has a significant influence on the rate of signal propagation along the axon. Expansion of axonal diameter is referred to as radial growth and is dependent upon both myelination and neurofilaments. Neurofilaments (NFs) are the most abundantly expressed cytoskeletal proteins in myelinated axons and consist of neurofilament light (NF-L), medium (NF-M), and heavy (NF-H) subunits. NF-M and NF-H were hypothesized to regulate axonal diameter through myelin-dependent phosphorylation of lysine-serine-proline (KSP) repeats. Gene deletion of NF-L suggested that NF-L is required for assembly of NF subunits into mature NFs. NF-H gene deletion resulted in small reductions in axonal diameter suggesting that NF-H was dispensable for radial axonal growth. Gene deletion of NF-M and its carboxy terminus (C-terminus) resulted in substantial reductions in axonal diameter and reduced nerve conduction velocity. However, prevention of NF-M KSP phosphorylation did not