αII-Spectrin Is Essential for Assembly of the Nodes of Ranvier in Myelinated Axons

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Abstract

Saltatory conduction in myelinated axons requires organization of the nodes of Ranvier, where voltage-gated sodium channels are prominently localized [1]. Previous results indicate that αII-spectrin, a component of the cortical cytoskeleton [2], is enriched at the paranodes [3, 4], which flank the node of Ranvier, but αII-spectrin's function has not been investigated. Starting with a genetic screen in zebrafish, we discovered in αII-spectrin (αII-spn) a mutation that disrupts nodal sodium-channel clusters in myelinated axons of the PNS and CNS. In αII-spn mutants, the nodal sodium-channel clusters are reduced in number and disrupted at early stages. Analysis of chimeric animals indicated that αII-spn functions autonomously in neurons. Ultrastructural studies show that myelin forms in the posterior lateral line nerve and in the ventral spinal cord in αII-spn mutants and that the node is abnormally long; these findings indicate that αII-spn is required for the assembly of a mature node of the correct length. We find that αII-spectrin is enriched in nodes and paranodes at early stages and that the nodal expression diminishes as nodes mature. Our results provide functional evidence that αII-spectrin in the axonal cytoskeleton is essential for stabilizing nascent sodium-channel clusters and assembling the mature node of Ranvier. © 2007 Elsevier Ltd. All rights reserved.

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Voas, M. G., Lyons, D. A., Naylor, S. G. G., Arana, N., Rasband, M. N. N., & Talbot, W. S. (2007). αII-Spectrin Is Essential for Assembly of the Nodes of Ranvier in Myelinated Axons. Current Biology, 17(6), 562–568. https://doi.org/10.1016/j.cub.2007.01.071

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