Abstract
Accumulation of Na(+) channels at the nodes of Ranvier is a prerequisite for saltatory conduction. In peripheral nerves, clustering of these channels along the axolemma is regulated by myelinating Schwann cells through a yet unknown mechanism. We report the identification of gliomedin, a glial ligand for neurofascin and NrCAM, two axonal immunoglobulin cell adhesion molecules that are associated with Na+ channels at the nodes of Ranvier. Gliomedin is expressed by myelinating Schwann cells and accumulates at the edges of each myelin segment during development, where it aligns with the forming nodes. Eliminating the expression of gliomedin by RNAi, or the addition of a soluble extracellular domain of neurofascin to myelinating cultures, which caused the redistribution of gliomedin along the internodes, abolished node formation. Furthermore, a soluble gliomedin induced nodal-like clusters of Na+ channels in the absence of Schwann cells. We propose that gliomedin provides a glial cue for the formation of peripheral nodes of Ranvier.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Age Factors
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Amino Acid Sequence
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Animals
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Ankyrins / metabolism
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Axons / metabolism*
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Blotting, Northern / methods
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Blotting, Western / methods
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Cell Adhesion Molecules / immunology
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Cell Adhesion Molecules / metabolism*
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Cell Adhesion Molecules, Neuronal / metabolism
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Cell Compartmentation
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Cells, Cultured
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Chlorocebus aethiops
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Claudins
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Cloning, Molecular / methods
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Cytoskeletal Proteins
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Fluorescent Antibody Technique / methods
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Ganglia, Spinal / metabolism
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Gene Expression Regulation, Developmental
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Humans
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Macromolecular Substances / immunology
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Macromolecular Substances / metabolism*
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Membrane Proteins / metabolism
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Microfilament Proteins / metabolism
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Microscopy, Immunoelectron / methods
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Myelin Basic Protein / metabolism
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Myelin-Associated Glycoprotein / metabolism
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Neurofilament Proteins / metabolism
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Phosphoproteins / metabolism
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Protein Binding / physiology
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Protein Structure, Tertiary
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Ranvier's Nodes / metabolism*
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Ranvier's Nodes / ultrastructure
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Rats
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Receptors, Peptide / metabolism
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S100 Proteins / metabolism
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Schwann Cells / metabolism*
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Schwann Cells / ultrastructure
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Sciatic Nerve / growth & development
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Sciatic Nerve / metabolism
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Sodium Channels / metabolism
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Spectrin / metabolism
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Transfection / methods
Substances
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Ank3 protein, rat
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Ankyrins
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Cell Adhesion Molecules
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Cell Adhesion Molecules, Neuronal
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Claudins
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Cldn2 protein, rat
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Cntnap1 protein, rat
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Cytoskeletal Proteins
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Macromolecular Substances
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Membrane Proteins
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Microfilament Proteins
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Myelin Basic Protein
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Myelin-Associated Glycoprotein
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Neurofilament Proteins
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Phosphoproteins
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Receptors, Peptide
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S100 Proteins
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Sodium Channels
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alpha-latrotoxin receptor
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ezrin
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gliomedin, rat
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Spectrin
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moesin