Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Binding Sites / physiology
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COS Cells
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Caenorhabditis elegans Proteins*
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Calcium-Calmodulin-Dependent Protein Kinases*
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Cell Membrane / physiology
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Cell Polarity / physiology
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Guanylate Kinases
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Helminth Proteins / chemistry
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Helminth Proteins / genetics*
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Helminth Proteins / metabolism*
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Kidney Tubules, Collecting / cytology
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Ligands
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Membrane Proteins / chemistry
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Membrane Proteins / genetics*
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Membrane Proteins / metabolism*
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Molecular Sequence Data
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Nucleoside-Phosphate Kinase / chemistry
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Nucleoside-Phosphate Kinase / genetics*
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Nucleoside-Phosphate Kinase / metabolism*
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Oocytes / physiology
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Patch-Clamp Techniques
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Potassium / metabolism
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Potassium Channels / chemistry
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Potassium Channels / genetics*
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Potassium Channels / metabolism*
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Precipitin Tests
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Protein Structure, Tertiary
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Protein Transport / physiology
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Sequence Homology, Amino Acid
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Two-Hybrid System Techniques
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Xenopus laevis
Substances
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Caenorhabditis elegans Proteins
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Helminth Proteins
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LIN-7 protein, C elegans
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Ligands
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Membrane Proteins
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Potassium Channels
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CASK kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Nucleoside-Phosphate Kinase
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Guanylate Kinases
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Potassium