title: Neurofascins are required to establish axonal domains for saltatory conduction.
abstract: Voltage-gated sodium channels are concentrated in myelinated nerves at the nodes of Ranvier flanked by paranodal axoglial junctions. Establishment of these essential nodal and paranodal domains is determined by myelin-forming glia, but the mechanisms are not clear. Here, we show that two isoforms of Neurofascin, Nfasc155 in glia and Nfasc186 in neurons, are required for the assembly of these specialized domains. In Neurofascin-null mice, neither paranodal adhesion junctions nor nodal complexes are formed. Transgenic expression of Nfasc155 in the myelinating glia of Nfasc-/- nerves rescues the axoglial adhesion complex by recruiting the axonal proteins Caspr and Contactin to the paranodes. However, in the absence of Nfasc186, sodium channels remain diffusely distributed along the axon. Our study shows that the two major Neurofascins play essential roles in assembling the nodal and paranodal domains of myelinated axons; therefore, they are essential for the transition to saltatory conduction in developing vertebrate nerves.
authors.affiliation: Centre for Neuroscience Research, University of Edinburgh, Edinburgh EH9 1QH, United Kingdom.
authors.forename: Diane L
authors.initials: DL
authors.lastname: Sherman
authors.forename: Steven
authors.initials: S
authors.lastname: Tait
authors.forename: Shona
authors.initials: S
authors.lastname: Melrose
authors.forename: Richard
authors.initials: R
authors.lastname: Johnson
authors.forename: Barbara
authors.initials: B
authors.lastname: Zonta
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Court
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Macklin
authors.forename: Stephen
authors.initials: S
authors.lastname: Meek
authors.forename: Andrew J H
authors.initials: AJ
authors.lastname: Smith
authors.forename: David F
authors.initials: DF
authors.lastname: Cottrell
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Brophy
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D005110:Extracellular Space; D007365:Intercellular Junctions / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D009414:Nerve Growth Factors / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009431:Neural Conduction / Q000502:physiology*; D009457:Neuroglia / Q000378:metabolism / Q000502:physiology; D010641:Phenotype; D020033:Protein Isoforms / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D011901:Ranvier's Nodes / Q000502:physiology; D015222:Sodium Channels / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; D009414:Nerve Growth Factors; C504593:Nfasc protein, mouse; D020033:Protein Isoforms; D015222:Sodium Channels