A unique sorting nexin regulates trafficking of potassium channels via a PDZ domain interaction.
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.
Lunn
Marie-Louise
ML
Peptide Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd., La Jolla, California 92037, USA.
Nassirpour
Rounak
R
Arrabit
Christine
C
Tan
Joshua
J
McLeod
Ian
I
Arias
Carlos M
CM
Sawchenko
Paul E
PE
Yates
John R
JR
Slesinger
Paul A
PA
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002461:Cell Line, Transformed; D004705:Endocytosis / Q000502:physiology; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D047468:Immunoprecipitation / Q000379:methods; D008297:Male; D008564:Membrane Potentials / Q000235:genetics; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000502:physiology*; D054731:PDZ Domains / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology; D040901:Proteomics; D051381:Rats; D014162:Transfection / Q000379:methods