A unique sorting nexin regulates trafficking of potassium channels via a PDZ domain interaction

Nat Neurosci. 2007 Oct;10(10):1249-59. doi: 10.1038/nn1953. Epub 2007 Sep 2.


G protein-gated potassium (Kir3) channels are important for controlling neuronal excitability in the brain. Using a proteomics approach, we have identified a unique rodent intracellular protein, sorting nexin 27 (SNX27), which regulates the trafficking of Kir3 channels. Like most sorting nexins, SNX27 possesses a functional PX domain that selectively binds the membrane phospholipid phosphatidylinositol-3-phosphate (PI3P) and is important for trafficking to the early endosome. SNX27, however, is the only sorting nexin to contain a PDZ domain. This PDZ domain discriminates between channels with similar class I PDZ-binding motifs, associating with the C-terminal end of Kir3.3 and Kir3.2c (-ESKV), but not with that of Kir2.1 (-ESEI) or Kv1.4 (-ETDV). SNX27 promotes the endosomal movement of Kir3 channels, leading to reduced surface expression, increased degradation and smaller Kir3 potassium currents. The regulation of endosomal trafficking via sorting nexins reveals a previously unknown mechanism for controlling potassium channel surface expression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / cytology
  • Brain / metabolism*
  • Cell Line, Transformed
  • Endocytosis / physiology
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / metabolism*
  • Gene Expression Regulation / genetics
  • Humans
  • Immunoprecipitation / methods
  • Male
  • Membrane Potentials / genetics
  • Molecular Sequence Data
  • Nerve Tissue Proteins / physiology*
  • PDZ Domains / physiology*
  • Patch-Clamp Techniques / methods
  • Protein Structure, Tertiary
  • Protein Transport / physiology
  • Proteomics
  • Rats
  • Transfection / methods


  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Nerve Tissue Proteins
  • Snx27 protein, rat