Identification of a conserved ankyrin-binding motif in the family of sodium channel alpha subunits

J Biol Chem. 2003 Jul 25;278(30):27333-9. doi: 10.1074/jbc.M303327200. Epub 2003 Apr 25.


Interactions with ankyrinG are crucial to the localization of voltage-gated sodium channels (VGSCs) at the axon initial segment and for neurons to initiate action potentials. However, the molecular nature of these interactions remains unclear. Here we report that VGSC-alpha, but not -beta, subunits bind to ankyrinG using pull-down assays. Further dissection of this activity identifies a conserved 9-amino acid motif ((V/A)P(I/L)AXXE(S/D)D) required for ankyrinG binding. This motif is also required for the localization of chimeric neurofascin/sodium channel molecules to the initial segment of cultured hippocampal neurons. The conserved nature of this motif suggests that it functions to localize sodium channels to a variety of "excitable" membrane domains both inside and outside of the nervous system.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Ankyrins / chemistry*
  • Ankyrins / metabolism
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / metabolism
  • Cell Line
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Cricetinae
  • DNA, Complementary / metabolism
  • Hippocampus / cytology
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Nerve Growth Factors / chemistry
  • Nerve Growth Factors / metabolism
  • Neurons / metabolism
  • Plasmids / metabolism
  • Protein Binding
  • Protein Structure, Tertiary
  • Rats
  • Rats, Wistar
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Sodium Channels / chemistry*
  • Transfection
  • Two-Hybrid System Techniques


  • Ankyrins
  • Cell Adhesion Molecules
  • DNA, Complementary
  • Nerve Growth Factors
  • Nfasc protein, rat
  • Recombinant Fusion Proteins
  • Sodium Channels