alphaII-spectrin is essential for assembly of the nodes of Ranvier in myelinated axons.
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.
Voas
Matthew G
MG
Department of Developmental Biology, Stanford University School of Medicine, 279 Campus Drive, Stanford, California 94305.
Lyons
David A
DA
Naylor
Stephen G
SG
Arana
Naomi
N
Rasband
Matthew N
MN
Talbot
William S
WS
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D008969:Molecular Sequence Data; D009154:Mutation; D011901:Ranvier's Nodes / Q000378:metabolism* / Q000648:ultrastructure; D015222:Sodium Channels / Q000378:metabolism; D013049:Spectrin / Q000235:genetics / Q000502:physiology*; D015027:Zebrafish / Q000378:metabolism*
D015222:Sodium Channels; D013049:Spectrin