Identification of a conserved ankyrin-binding motif in the family of sodium channel alpha subunits.
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.
Lemaillet
Guy
G
Department of Cell Biology and Program in Neuroscience, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Walker
Barbara
B
Lambert
Stephen
S
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D017487:Ankyrins / Q000737:chemistry* / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006224:Cricetinae; D018076:DNA, Complementary / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000737:chemistry / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015222:Sodium Channels / Q000737:chemistry*; D014162:Transfection; D020798:Two-Hybrid System Techniques
D017487:Ankyrins; D015815:Cell Adhesion Molecules; D018076:DNA, Complementary; D009414:Nerve Growth Factors; C504594:Nfasc protein, rat; D011993:Recombinant Fusion Proteins; D015222:Sodium Channels