Ras-association domain of sorting Nexin 27 is critical for regulating expression of GIRK potassium channels

PLoS One. 2013;8(3):e59800. doi: 10.1371/journal.pone.0059800. Epub 2013 Mar 25.


G protein-gated inwardly rectifying potassium (GIRK) channels play an important role in regulating neuronal excitability. Sorting nexin 27b (SNX27b), which reduces surface expression of GIRK channels through a PDZ domain interaction, contains a putative Ras-association (RA) domain with unknown function. Deleting the RA domain in SNX27b (SNX27b-ΔRA) prevents the down-regulation of GIRK2c/GIRK3 channels. Similarly, a point mutation (K305A) in the RA domain disrupts regulation of GIRK2c/GIRK3 channels and reduces H-Ras binding in vitro. Finally, the dominant-negative H-Ras (S17N) occludes the SNX27b-dependent decrease in surface expression of GIRK2c/GIRK3 channels. Thus, the presence of a functional RA domain and the interaction with Ras-like G proteins comprise a novel mechanism for modulating SNX27b control of GIRK channel surface expression and cellular excitability.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / genetics*
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / metabolism*
  • Gene Deletion
  • Gene Expression Regulation*
  • Humans
  • Molecular Sequence Data
  • Protein Binding
  • Protein Interaction Domains and Motifs* / genetics
  • Protein Transport
  • Proto-Oncogene Proteins p21(ras) / metabolism*
  • Sequence Alignment
  • Sorting Nexins / chemistry*
  • Sorting Nexins / genetics
  • Sorting Nexins / metabolism*


  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • KCNJ6 protein, human
  • SNX27 protein, human
  • Sorting Nexins
  • Proto-Oncogene Proteins p21(ras)