Glial and neuronal isoforms of Neurofascin have distinct roles in the assembly of nodes of Ranvier in the central nervous system.
Rapid nerve impulse conduction in myelinated axons requires the concentration of voltage-gated sodium channels at nodes of Ranvier. Myelin-forming oligodendrocytes in the central nervous system (CNS) induce the clustering of sodium channels into nodal complexes flanked by paranodal axoglial junctions. However, the molecular mechanisms for nodal complex assembly in the CNS are unknown. Two isoforms of Neurofascin, neuronal Nfasc186 and glial Nfasc155, are components of the nodal and paranodal complexes, respectively. Neurofascin-null mice have disrupted nodal and paranodal complexes. We show that transgenic Nfasc186 can rescue the nodal complex when expressed in Nfasc(-/-) mice in the absence of the Nfasc155-Caspr-Contactin adhesion complex. Reconstitution of the axoglial adhesion complex by expressing transgenic Nfasc155 in oligodendrocytes also rescues the nodal complex independently of Nfasc186. Furthermore, the Nfasc155 adhesion complex has an additional function in promoting the migration of myelinating processes along CNS axons. We propose that glial and neuronal Neurofascins have distinct functions in the assembly of the CNS node of Ranvier.
Centre for Neuroscience Research, Royal Dick School of Veterinary Studies, University of Edinburgh, Edinburgh EH9 1QH, Scotland, UK.
Barbara
B
Zonta
Steven
S
Tait
Shona
S
Melrose
Heather
H
Anderson
Sheila
S
Harroch
Jennifer
J
Higginson
Diane L
DL
Sherman
Peter J
PJ
Brophy
D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000172:deficiency / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002465:Cell Movement; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D058966:Contactins; D051379:Mice; D008810:Mice, Inbred C57BL; D050505:Mutant Proteins / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism / Q000648:ultrastructure; D009414:Nerve Growth Factors / Q000172:deficiency / Q000378:metabolism*; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D010641:Phenotype; D020033:Protein Isoforms / Q000378:metabolism; D011901:Ranvier's Nodes / Q000378:metabolism* / Q000648:ultrastructure; D015222:Sodium Channels / Q000378:metabolism
D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; C491322:Cntnap1 protein, mouse; D058966:Contactins; D050505:Mutant Proteins; D009414:Nerve Growth Factors; C504593:Nfasc protein, mouse; D020033:Protein Isoforms; D015222:Sodium Channels