Neurofascins are required to establish axonal domains for saltatory conduction.
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.
Sherman
Diane L
DL
Centre for Neuroscience Research, University of Edinburgh, Edinburgh EH9 1QH, United Kingdom.
Tait
Steven
S
Melrose
Shona
S
Johnson
Richard
R
Zonta
Barbara
B
Court
Felipe A
FA
Macklin
Wendy B
WB
Meek
Stephen
S
Smith
Andrew J H
AJ
Cottrell
David F
DF
Brophy
Peter J
PJ
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*
D015815:Cell Adhesion Molecules; D009414:Nerve Growth Factors; C504593:Nfasc protein, mouse; D020033:Protein Isoforms; D015222:Sodium Channels