Basolateral membrane expression of the Kir 2.3 channel is coordinated by PDZ interaction with Lin-7/CASK complex

• Published in: American Journal of Physiology: Cell Physiology 2002-01, Vol.282 (1), p.C183-C195
• Main Authors: Olsen, Olav, Liu, Hui, Wade, James B, Merot, Jean, Welling, Paul A
• Format: Article
• Language: English
• Subjects: Animals; Binding Sites - physiology; Caenorhabditis elegans Proteins; Calcium-Calmodulin-Dependent Protein Kinases; Cell Membrane - physiology; Cell Polarity - physiology; COS Cells; Guanylate Kinases; Helminth Proteins - chemistry; Helminth Proteins - genetics; Helminth Proteins - metabolism; Kidney Tubules, Collecting - cytology; Ligands; Membrane Proteins - chemistry; Membrane Proteins - genetics; Membrane Proteins - metabolism; Molecular Sequence Data; Nucleoside-Phosphate Kinase - chemistry; Nucleoside-Phosphate Kinase - genetics; Nucleoside-Phosphate Kinase - metabolism; Oocytes - physiology; Patch-Clamp Techniques; Potassium - metabolism; Potassium Channels - chemistry; Potassium Channels - genetics; Potassium Channels - metabolism; Precipitin Tests; Protein Structure, Tertiary; Protein Transport - physiology; Sequence Homology, Amino Acid; Two-Hybrid System Techniques; Xenopus laevis
• ISSN: 0363-6143; 1522-1563
• DOI: 10.1152/ajpcell.00249.2001

1  Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland 21201; and 2  Departement de Biologie Cellular et Moleculaire, Commissariate Energie Atomique, Saclay 91191, Gif Yvette, France The basolateral membrane sorting determinant of an inwardly rectifying potassium channel, Kir 2.3, is comprised of a unique arrangement of trafficking motifs containing tandem, conceivably overlapping, biosynthetic targeting and PDZ-based signals. In the present study, we elucidate a mechanism by which a PDZ interaction coordinates one step in a basolateral membrane sorting program. In contrast to apical missorting of channels lacking the entire sorting domain, deletion of the PDZ binding motif caused channels to accumulate into an endosomal compartment. Here, we identify a new human ortholog of a Caenorhabditis elegans PDZ protein, hLin-7b, that interacts with the COOH-terminal tail of Kir 2.3   in renal epithelia. hLin-7b associates with the channel as a part of a multimeric complex on the basolateral membrane similar to a basolateral membrane complex in C. elegans vulva progenitor cells. Coexpression of hLin-7b with Kir 2.3 dramatically increases channel activity by stabilizing plasma membrane expression. The discovery identifies one component of the sorting machinery and provides evidence for a retention mechanism in a hierarchical basolateral trafficking program. polarity; membrane trafficking; intracellular sorting mechanism; protein-protein interaction; potassium; inward rectification; cortical collecting duct