A targeting motif involved in sodium channel clustering at the axonal initial segment

Science. 2003 Jun 27;300(5628):2091-4. doi: 10.1126/science.1085167.

Abstract

The sorting of sodium channels to axons and the formation of clusters are of primary importance for neuronal electrogenesis. Here, we showed that the cytoplasmic loop connecting domains II and III of the Nav1 subunit contains a determinant conferring compartmentalization in the axonal initial segment of rat hippocampal neurons. Expression of a soluble Nav1.2II-III linker protein led to the disorganization of endogenous sodium channels. The motif was sufficient to redirect a somatodendritic potassium channel to the axonal initial segment, a process involving association with ankyrin G. Thus, this motif may play a fundamental role in controlling electrical excitability during development and plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Ankyrins / metabolism
  • Axons / metabolism*
  • Cell Membrane / metabolism
  • Delayed Rectifier Potassium Channels
  • Hippocampus / cytology
  • Humans
  • Ion Channel Gating
  • Molecular Sequence Data
  • Mutation
  • NAV1.2 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins / chemistry*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / metabolism
  • Patch-Clamp Techniques
  • Potassium Channels / metabolism
  • Potassium Channels, Voltage-Gated*
  • Protein Structure, Tertiary
  • Protein Transport
  • Rats
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Sodium Channels / chemistry*
  • Sodium Channels / genetics
  • Sodium Channels / metabolism*
  • Transfection

Substances

  • Ankyrins
  • Delayed Rectifier Potassium Channels
  • NAV1.2 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Recombinant Fusion Proteins
  • SCN2A protein, human
  • Scn2A protein, rat
  • Sodium Channels