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An apical PDZ protein anchors the cystic fibrosis transmembrane conductance regulator to the cytoskeleton.

The function of the cystic fibrosis transmembrane conductance regulator (CFTR) as a Cl- channel in the apical membrane of epithelial cells is extensively documented. However, less is known about the molecular determinants of CFTR residence in the apical membrane, basal regulation of its Cl- channel activity, and its reported effects on the function of other transporters. These aspects of CFTR function likely require specific interactions between CFTR and unknown proteins in the apical compartment of epithelial cells. Here we report that CFTR interacts with the recently discovered protein, EBP50 (ERM-binding phosphoprotein 50). EBP50 is concentrated at the apical membrane in human airway epithelial cells, in vivo, and CFTR and EBP50 associate in in vitro binding assays. The CFTR-EBP50 interaction requires the COOH-terminal DTRL sequence of CFTR and utilizes either PDZ1 or PDZ2 of EBP50, although binding to PDZ1 is of greater affinity. Through formation of a complex, the interaction between CFTR and EBP50 may influence the stability and/or regulation of CFTR Cl- channel function in the cell membrane and provides a potential mechanism through which CFTR can affect the activity of other apical membrane proteins.

Pubmed ID: 9677412


  • Short DB
  • Trotter KW
  • Reczek D
  • Kreda SM
  • Bretscher A
  • Boucher RC
  • Stutts MJ
  • Milgram SL


The Journal of biological chemistry

Publication Data

July 31, 1998

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM36652
  • Agency: NHLBI NIH HHS, Id: P50 HL42384
  • Agency: NIDDK NIH HHS, Id: R29DK50744

Mesh Terms

  • Amino Acid Sequence
  • Biosensing Techniques
  • Bronchi
  • Carrier Proteins
  • Cell Line
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Cytoskeletal Proteins
  • Fluorescent Antibody Technique
  • Humans
  • Membrane Proteins
  • Molecular Sequence Data
  • Peptide Fragments
  • Phosphoproteins
  • Protein Binding
  • Sodium-Hydrogen Antiporter