title: Phosphorylation of highly conserved neurofilament medium KSP repeats is not required for myelin-dependent radial axonal growth.
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.
authors.affiliation: Department of Biological Sciences, Bond Life Sciences Center, University of Missouri-Columbia, Columbia, Missouri 65211, USA.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Garcia
authors.forename: Mala V
authors.initials: MV
authors.lastname: Rao
authors.forename: Jiro
authors.initials: J
authors.lastname: Fujimoto
authors.forename: Virginia B
authors.initials: VB
authors.lastname: Garcia
authors.forename: Sameer B
authors.initials: SB
authors.lastname: Shah
authors.forename: John
authors.initials: J
authors.lastname: Crum
authors.forename: Takahiro
authors.initials: T
authors.lastname: Gotow
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Uchiyama
authors.forename: Mark
authors.initials: M
authors.lastname: Ellisman
authors.forename: Nigel A
authors.initials: NA
authors.lastname: Calcutt
authors.forename: Don W
authors.initials: DW
authors.lastname: Cleveland
mesh_terms: D000409:Alanine / Q000235:genetics; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D017124:Conserved Sequence / Q000235:genetics; D055879:Gene Knock-In Techniques; D008239:Lysine / Q000378:metabolism; D051379:Mice; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009409:Nerve Crush; D009434:Neural Pathways / Q000502:physiology; D016900:Neurofilament Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation / Q000235:genetics; D011392:Proline / Q000378:metabolism; D020449:Repetitive Sequences, Amino Acid / Q000235:genetics; D012694:Serine / Q000235:genetics
chemical_list: D016900:Neurofilament Proteins; C061195:neurofilament protein M; D012694:Serine; D011392:Proline; D008239:Lysine; D000409:Alanine