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