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.
Department of Physiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
D B
DB
Short
K W
KW
Trotter
D
D
Reczek
S M
SM
Kreda
A
A
Bretscher
R C
RC
Boucher
M J
MJ
Stutts
S L
SL
Milgram
D000595:Amino Acid Sequence; D015374:Biosensing Techniques; D001980:Bronchi / Q000166:cytology; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D017923:Sodium-Hydrogen Exchangers; D000099149:Ezrin
D002352:Carrier Proteins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D010446:Peptide Fragments; D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; D000099149:Ezrin; C505032:CFTR protein, human; C093376:sodium-hydrogen exchanger regulatory factor