Neurofascins are required to establish axonal domains for saltatory conduction

Diane L Sherman, Steven Tait, Shona Melrose, Richard Johnson, Barbara Zonta, Felipe A Court, Wendy B Macklin, Stephen Meek, Andrew J H Smith, David F Cottrell, Peter J Brophy

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)737-42
Number of pages6
JournalNeuron
Volume48
Issue number5
DOIs
Publication statusPublished - 2005

Keywords

  • Animals
  • Axons/physiology
  • Cell Adhesion Molecules/chemistry
  • Cell Adhesion Molecules/deficiency
  • Cell Adhesion Molecules/genetics
  • Cell Adhesion Molecules/physiology
  • Extracellular Space
  • Intercellular Junctions/physiology
  • Mice
  • Mice, Knockout/genetics
  • Mice, Transgenic
  • Myelin Sheath/metabolism
  • Nerve Fibers, Myelinated/physiology
  • Nerve Growth Factors/chemistry
  • Nerve Growth Factors/deficiency
  • Nerve Growth Factors/genetics
  • Nerve Growth Factors/physiology
  • Neural Conduction/physiology
  • Neuroglia/metabolism
  • Neuroglia/physiology
  • Phenotype
  • Protein Isoforms/deficiency
  • Protein Isoforms/genetics
  • Protein Isoforms/physiology
  • Protein Structure, Tertiary/physiology
  • Ranvier's Nodes/physiology
  • Sodium Channels/physiology

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