Leading science, pioneering therapies
CRM Publications

Neurofascins are required to establish axonal domains for saltatory conduction.

TitleNeurofascins are required to establish axonal domains for saltatory conduction.
Publication TypeJournal Article
Year of Publication2005
AuthorsSherman DL, Tait S, Melrose S, Johnson R, Zonta B, Court FA, Macklin WB, Meek S, Smith AG, Cottrell DF, Brophy PJ
JournalNeuron
Volume48
Issue5
Pagination737-42
Date Published2005 Dec 8
ISSN0896-6273
KeywordsAnimals, Axons, Cell Adhesion Molecules, Extracellular Space, Intercellular Junctions, Mice, Mice, Knockout, Mice, Transgenic, Myelin Sheath, Nerve Fibers, Myelinated, Nerve Growth Factors, Neural Conduction, Neuroglia, Phenotype, Protein Isoforms, Protein Structure, Tertiary, Ranvier's Nodes, Sodium Channels
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.

DOI10.1016/j.neuron.2005.10.019
Alternate JournalNeuron
PubMed ID16337912
Grant List669 / / Multiple Sclerosis Society / United Kingdom
G0000221 / / Medical Research Council / United Kingdom
G0301172 / / Medical Research Council / United Kingdom
/ / Wellcome Trust / United Kingdom