title: A unique sorting nexin regulates trafficking of potassium channels via a PDZ domain interaction.
abstract: 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.
authors.affiliation: Peptide Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd., La Jolla, California 92037, USA.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Lunn
authors.forename: Rounak
authors.initials: R
authors.lastname: Nassirpour
authors.forename: Christine
authors.initials: C
authors.lastname: Arrabit
authors.forename: Joshua
authors.initials: J
authors.lastname: Tan
authors.forename: Ian
authors.initials: I
authors.lastname: McLeod
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Arias
authors.forename: Paul E
authors.initials: PE
authors.lastname: Sawchenko
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Paul A
authors.initials: PA
authors.lastname: Slesinger
mesh_terms: 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