TY - JOUR
T1 - Nodes of ranvier act as barriers to restrict invasion of flanking paranodal domains in myelinated axons
AU - Thaxton, Courtney
AU - Pillai, Anilkumar M.
AU - Pribisko, Alaine L.
AU - Dupree, Jeffrey L.
AU - Bhat, Manzoor A.
N1 - Funding Information:
We are grateful to Michael Sendtner, William Snider, Klaus Nave, and Victoria Bautch for generously sharing the Nefl-Cre, Tau mGFP/LacZ , Cnp-Cre, and R26R LacZ mice, respectively, and Matt Rasband for sharing the anti-FIGQY antibody. We thank Alan Fanning, Alex Gow, Lori Isom, and Stephen Lambert for comments on the manuscript, and Matt Rasband for helpful discussions. We also thank anonymous reviewers for their many insightful comments and suggestions, which led to a broader discussion of our in vivo findings. This work was supported by NIH grants GM063074 and NS050356, the National Multiple Sclerosis Society, and the State of North Carolina (M.A.B.).
PY - 2011/1/27
Y1 - 2011/1/27
N2 - Accumulation of voltage-gated sodium (Nav) 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 (NfascNF186) in vivo results in nodal disorganization, including loss of Nav 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 NfascNF186 mutant axons and occlude node formation. Our results suggest that NfascNF186-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.
AB - Accumulation of voltage-gated sodium (Nav) 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 (NfascNF186) in vivo results in nodal disorganization, including loss of Nav 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 NfascNF186 mutant axons and occlude node formation. Our results suggest that NfascNF186-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.
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U2 - 10.1016/j.neuron.2010.12.016
DO - 10.1016/j.neuron.2010.12.016
M3 - Article
C2 - 21262464
AN - SCOPUS:78751696198
SN - 0896-6273
VL - 69
SP - 244
EP - 257
JO - Neuron
JF - Neuron
IS - 2
ER -