ZFIN ID: ZDB-PUB-070303-44
alphaII-Spectrin Is Essential for Assembly of the Nodes of Ranvier in Myelinated Axons
Voas, M.G., Lyons, D.A., Naylor, S.G., Arana, N., Rasband, M.N., and Talbot, W.S.
Date: 2007
Source: Current biology : CB   17(6): 562-568 (Journal)
Registered Authors: Arana, Naomi, Lyons, David A., Naylor, Stephen, Talbot, William S., Voas, Matthew G.
Keywords: none
MeSH Terms:
  • Animals
  • Axons/metabolism*
  • Axons/ultrastructure
  • Microscopy, Electron, Transmission
  • Molecular Sequence Data
  • Mutation
  • Ranvier's Nodes/metabolism*
  • Ranvier's Nodes/ultrastructure
  • Sodium Channels/metabolism
  • Spectrin/genetics
  • Spectrin/physiology*
  • Zebrafish/metabolism*
PubMed: 17331725 Full text @ Curr. Biol.
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 alphaII-spectrin, a component of the cortical cytoskeleton [2], is enriched at the paranodes [3, 4], which flank the node of Ranvier, but alphaII-spectrin's function has not been investigated. Starting with a genetic screen in zebrafish, we discovered in alphaII-spectrin (alphaII-spn) a mutation that disrupts nodal sodium-channel clusters in myelinated axons of the PNS and CNS. In alphaII-spn mutants, the nodal sodium-channel clusters are reduced in number and disrupted at early stages. Analysis of chimeric animals indicated that alphaII-spn functions autonomously in neurons. Ultrastructural studies show that myelin forms in the posterior lateral line nerve and in the ventral spinal cord in alphaII-spn mutants and that the node is abnormally long; these findings indicate that alphaII-spn is required for the assembly of a mature node of the correct length. We find that alphaII-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 alphaII-spectrin in the axonal cytoskeleton is essential for stabilizing nascent sodium-channel clusters and assembling the mature node of Ranvier.