Demonstration that CFTR is a Chloride Channel by Alteration of its Anion Selectivity

Expression of the cystic fibrosis transmembrane conductance regulator (CFTR) generates adenosine 3′,5′-monophosphate (cAMP)-regulated chloride channels, indicating that CFTR is either a chloride channel or a chloride channel regulator. To distinguish between these possibilities, basic amino acids in...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1991-07, Vol.253 (5016), p.202-205
Main Authors: Anderson, Matthew P., Gregory, Richard J., Thompson, Simon, Souza, David W., Paul, Sucharita, Mulligan, Richard C., Smith, Alan E., Welsh, Michael J.
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amino acids
Anions
Biological and medical sciences
Cell lines
Cellular biology
Chloride Channels
Chlorides - physiology
chlorine
Cyclic AMP - physiology
Cystic fibrosis
Cystic Fibrosis - physiopathology
Cystic Fibrosis Transmembrane Conductance Regulator
DNA Mutational Analysis
Electric Conductivity
Electric potential
Epithelial cells
Gastroenterology. Liver. Pancreas. Abdomen
Genetic mutation
HeLa Cells
Humans
In Vitro Techniques
Ion Channels - genetics
Ion Channels - physiology
Liver. Biliary tract. Portal circulation. Exocrine pancreas
Medical research
Medical sciences
Membrane Glycoproteins - genetics
Membrane Glycoproteins - physiology
Membrane Potentials
membrane proteins
Membrane Proteins - genetics
Membrane Proteins - physiology
Molecular Sequence Data
Other diseases. Semiology
P branes
Physiological aspects
String theory
Transfection
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Description
Summary:Expression of the cystic fibrosis transmembrane conductance regulator (CFTR) generates adenosine 3′,5′-monophosphate (cAMP)-regulated chloride channels, indicating that CFTR is either a chloride channel or a chloride channel regulator. To distinguish between these possibilities, basic amino acids in the putative transmembrane domains were mutated. The sequence of anion selectivity of cAMP-regulated channels in cells containing either endogenous or recombinant CFTR was bromide > chloride > iodide > fluoride. Mutation of the lysines at positions 95 or 335 to acidic amino acids converted the selectivity sequence to iodide > bromide > chloride > fluoride. These data indicate that CFTR is a cAMP-regulated chloride channel and that lysines 95 and 335 determine anion selectivity.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1712984