First Author | Garcia ML | Year | 2009 |
Journal | J Neurosci | Volume | 29 |
Issue | 5 | Pages | 1277-84 |
PubMed ID | 19193875 | Mgi Jnum | J:155659 |
Mgi Id | MGI:4414927 | Doi | 10.1523/JNEUROSCI.3765-08.2009 |
Citation | Garcia ML, et al. (2009) Phosphorylation of highly conserved neurofilament medium KSP repeats is not required for myelin-dependent radial axonal growth. J Neurosci 29(5):1277-84 |
abstractText | Neurofilament medium (NF-M) is essential for the acquisition of normal axonal caliber in response to a myelin-dependent 'outside-in' trigger for radial axonal growth. Removal of the tail domain and lysine-serine-proline (KSP) repeats of NF-M, but not neurofilament heavy, produced axons with impaired radial growth and reduced conduction velocities. These earlier findings supported myelin-dependent phosphorylation of NF-M KSP repeats as an essential component of axonal growth. As a direct test of whether phosphorylation of NF-M KSP repeats is the target for the myelin-derived signal, gene replacement has now been used to produce mice in which all serines of NF-M's KSP repeats have been replaced with phosphorylation-incompetent alanines. This substitution did not alter accumulation of the neurofilaments or their subunits. Axonal caliber and motor neuron conduction velocity of mice expressing KSP phospho-incompetent NF-M were also indistinguishable from wild-type mice. Thus, phosphorylation of NF-M KSP repeats is not an essential component for the acquisition of normal axonal caliber mediated by myelin-dependent outside-in signaling. |