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J Biol Chem. 2003 Jul 25;278(30):27333-9. Epub 2003 Apr 25.

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

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  • 1Department of Cell Biology and Program in Neuroscience, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.


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.

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