1. Phosphorylation of highly conserved neurofilament medium KSP repeats is not required for myelin-dependent radial axonal growth.
- Author
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Garcia ML, Rao MV, Fujimoto J, Garcia VB, Shah SB, Crum J, Gotow T, Uchiyama Y, Ellisman M, Calcutt NA, and Cleveland DW
- Subjects
- Alanine genetics, Amino Acid Sequence, Amino Acid Substitution genetics, Animals, Axons metabolism, Axons ultrastructure, Gene Knock-In Techniques, Mice, Mice, Neurologic Mutants, Molecular Sequence Data, Myelin Sheath genetics, Myelin Sheath metabolism, Nerve Crush, Neural Pathways physiology, Neurofilament Proteins genetics, Neurofilament Proteins metabolism, Phosphorylation genetics, Axons physiology, Conserved Sequence genetics, Lysine metabolism, Myelin Sheath physiology, Neurofilament Proteins physiology, Proline metabolism, Repetitive Sequences, Amino Acid genetics, Serine genetics
- Abstract
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.
- Published
- 2009
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