Differential stability of PNS and CNS nodal complexes when neuronal neurofascin is lost.
Fast, saltatory conduction in myelinated nerves requires the clustering of voltage-gated sodium channels (Nav) at nodes of Ranvier in a nodal complex. The Neurofascin (Nfasc) gene encodes neuronal Neurofascin 186 (Nfasc186) at the node and glial Neurofascin 155 at the paranode, and these proteins play a key role in node assembly. However, their role in the maintenance and stability of the node is less well understood. Here we show that by inducible ablation of Nfasc in neurons in adult mice, Nfasc186 expression is reduced by >99% and 94% at PNS and CNS nodes, respectively. Gliomedin and NrCAM at PNS and brevican at CNS nodes are largely lost with neuronal neurofascin; however, Nav at nodes of Ranvier persist, albeit with ∼40% reduction in expression levels. βIV Spectrin, ankyrin G, and, to a lesser extent, the β1 subunit of the sodium channel, are less affected at the PNS node than in the CNS. Nevertheless, there is a 38% reduction in PNS conduction velocity. Loss of Nfasc186 provokes CNS paranodal disorganization, but this does not contribute to loss of Nav. These results show that Nav at PNS nodes are still maintained in a nodal complex when neuronal neurofascin is depleted, whereas the retention of nodal Nav in the CNS, despite more extensive dissolution of the complex, suggests a supportive role for the partially disrupted paranodal axoglial junction in selectively maintaining Nav at the CNS node.
Centre for Neuroregeneration, University of Edinburgh, Edinburgh EH16 4SB, United Kingdom.
Anne
A
Desmazieres
Barbara
B
Zonta
Ao
A
Zhang
Lai-Man N
LM
Wu
Diane L
DL
Sherman
Peter J
PJ
Brophy
D000818:Animals; D058581:Brevican / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D008297:Male; D051379:Mice; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D009457:Neuroglia / Q000378:metabolism; D021381:Protein Transport; D011901:Ranvier's Nodes / Q000378:metabolism*; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism
D058581:Brevican; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D009414:Nerve Growth Factors; C504593:Nfasc protein, mouse; C491151:Nrcam protein, mouse; D061566:Voltage-Gated Sodium Channels; C520020:gliomedin protein, mouse
myelination; neurofascin; nodes of Ranvier; sodium channels