Regulation of plasma membrane recycling by CFTR.
The gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) is defective in patients with cystic fibrosis. Although the protein product of the CFTR gene has been proposed to function as a chloride ion channel, certain aspects of its function remain unclear. The role of CFTR in the adenosine 3',5'-monophosphate (cAMP)-dependent regulation of plasma membrane recycling was examined. Adenosine 3',5'-monophosphate is known to regulate endocytosis and exocytosis in chloride-secreting epithelial cells that express CFTR. However, mutant epithelial cells derived from a patient with cystic fibrosis exhibited no cAMP-dependent regulation of endocytosis and exocytosis until they were transfected with complementary DNA encoding wild-type CFTR. Thus, CFTR is critical for cAMP-dependent regulation of membrane recycling in epithelial tissues, and this function of CFTR could explain in part the pleiotropic nature of cystic fibrosis.
Bradbury
N A
NA
Department of Physiology and Biophysics, University of Alabama, Birmingham 35294.
Jilling
T
T
Berta
G
G
Sorscher
E J
EJ
Bridges
R J
RJ
Kirk
K L
KL
D001483:Base Sequence; D002462:Cell Membrane / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000503:physiopathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004247:DNA / Q000235:genetics; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology; D004848:Epithelium / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression; D006735:Horseradish Peroxidase / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms; D014162:Transfection; D014407:Tumor Cells, Cultured; D014909:Wheat Germ Agglutinins / Q000378:metabolism
C505032:CFTR protein, human; D002712:Chlorides; D008565:Membrane Proteins; D014909:Wheat Germ Agglutinins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005576:Colforsin; D004247:DNA; D000242:Cyclic AMP; D006735:Horseradish Peroxidase