Article abstract
Nature Neuroscience 10, 1249 - 1259 (2007)
Published online: 2 September 2007 | doi:10.1038/nn1953
A unique sorting nexin regulates trafficking of potassium channels via a PDZ domain interaction
Marie-Louise Lunn1,5,6, Rounak Nassirpour1,2,6, Christine Arrabit1, Joshua Tan1, Ian Mcleod3, Carlos M Arias4, Paul E Sawchenko4, John R Yates, III3 & Paul A Slesinger1,2
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.
- Peptide Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd., La Jolla, California 92037, USA.
- Departments of Neurosciences and Biology, University of California, San Diego, La Jolla, California, 92093, USA.
- Department of Cell Biology, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, California 92037, USA.
- Neuronal Structure and Function Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Rd., La Jolla, California 92037, USA.
- Present address: Exiqon A/S, Bygstubben 9, DK-2950 Vedbaek, Denmark.
- These authors contributed equally to this work.
Correspondence to: Paul A Slesinger1,2 e-mail: slesinger@salk.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
NMDA receptor trafficking through an interaction between PDZ proteins and the exocyst complexNature Cell Biology Article (01 Jun 2003)
Molecular determinants of NMDA receptor internalizationNature Neuroscience Article (01 Aug 2001)
Human papillomavirus type 16 E6 protein interacts with cystic fibrosis transmembrane regulator-associated ligand and promotes E6-associated protein-mediated ubiquitination and proteasomal degradationOncogene Original Article
See all 67 matches for Research
