Schwann cells inhibit ectopic clustering of axonal sodium channels.
The clustering of voltage-gated sodium channels at the axon initial segment (AIS) and nodes of Ranvier is essential for the initiation and propagation of action potentials in myelinated axons. Sodium channels localize to the AIS through an axon-intrinsic mechanism driven by ankyrin G, while clustering at the nodes requires cues from myelinating glia that interact with axonal neurofascin186 (Sherman et al., 2005; Dzhashiashvili et al., 2007; Yang et al., 2007). Here, we report that in zebrafish mutants lacking Schwann cells in peripheral nerves (erbb2, erbb3, and sox10/colorless), axons form numerous aberrant sodium channel clusters throughout their length. Morpholino knockdown of ankyrin G, but not neurofascin, reduces the number of sodium channel clusters in Schwann cell-deficient mutants, suggesting that these aberrant clusters form by an axon-intrinsic mechanism. We also find that gpr126 mutants, in which Schwann cells are arrested at the promyelinating stage (Monk et al., 2009), are deficient in the clustering of neurofascin at the nodes of Ranvier. When Schwann cell migration in gpr126 mutants is blocked, there is an increase in the number of neurofascin clusters in peripheral axons. Our results suggest that Schwann cells inhibit the ability of ankyrin G to cluster sodium channels at ectopic locations, restricting its activity to the AIS and nodes of Ranvier.
Voas
Matthew G
MG
Department of Developmental Biology, Stanford University School of Medicine, Stanford, California 94305, USA.
Glenn
Thomas D
TD
Raphael
Alya R
AR
Talbot
William S
WS
D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000648:ultrastructure; D009433:Neural Inhibition / Q000235:genetics / Q000502:physiology*; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D011901:Ranvier's Nodes / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D012583:Schwann Cells / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism* / Q000648:ultrastructure
D009419:Nerve Tissue Proteins; D015222:Sodium Channels; D029961:Zebrafish Proteins