Nodes of Ranvier act as barriers to restrict invasion of flanking paranodal domains in myelinated axons.
Accumulation of voltage-gated sodium (Na(v)) channels at nodes of Ranvier is paramount for action potential propagation along myelinated fibers, yet the mechanisms governing nodal development, organization, and stabilization remain unresolved. Here, we report that genetic ablation of the neuron-specific isoform of Neurofascin (Nfasc(NF¹⁸⁶)) in vivo results in nodal disorganization, including loss of Na(v) channel and ankyrin-G (AnkG) enrichment at nodes in the peripheral nervous system (PNS) and central nervous system (CNS). Interestingly, the presence of paranodal domains failed to rescue nodal organization in the PNS and the CNS. Most importantly, using ultrastructural analysis, we demonstrate that the paranodal domains invade the nodal space in Nfasc(NF¹⁸⁶) mutant axons and occlude node formation. Our results suggest that Nfasc(NF¹⁸⁶)-dependent assembly of the nodal complex acts as a molecular boundary to restrict the movement of flanking paranodal domains into the nodal area, thereby facilitating the stereotypic axonal domain organization and saltatory conduction along myelinated axons.
Department of Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, Chapel Hill, NC 27599-7545, USA.
Courtney
C
Thaxton
Anilkumar M
AM
Pillai
Alaine L
AL
Pribisko
Jeffrey L
JL
Dupree
Manzoor A
MA
Bhat
D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002490:Central Nervous System / Q000033:anatomy & histology / Q000473:pathology / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009413:Nerve Fibers, Myelinated / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure*; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D009431:Neural Conduction / Q000502:physiology; D017933:Peripheral Nervous System / Q000033:anatomy & histology / Q000473:pathology / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011901:Ranvier's Nodes / Q000473:pathology / Q000502:physiology* / Q000648:ultrastructure*; D015222:Sodium Channels / Q000378:metabolism*
D015815:Cell Adhesion Molecules; D009414:Nerve Growth Factors; C504593:Nfasc protein, mouse; D020033:Protein Isoforms; D015222:Sodium Channels
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