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Proc Natl Acad Sci U S A
1999 Apr 27;969:5310-5. doi: 10.1073/pnas.96.9.5310.
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The first-nucleotide binding domain of the cystic-fibrosis transmembrane conductance regulator is important for inhibition of the epithelial Na+ channel.
Schreiber R
,
Hopf A
,
Mall M
,
Greger R
,
Kunzelmann K
.
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The cystic-fibrosis transmembrane conductance regulator (CFTR) functions as a cAMP-regulated Cl- channel and as a regulator of other membrane conductances. cAMP-dependent activation of CFTR inhibits epithelial Na+ channels (ENaC). The specificity of interaction between CFTR and ENaC was examined by coexpression of ENaC and ATP-binding cassette (ABC) proteins other than CFTR. In addition, we identified domains within CFTR that are of particular importance for the inhibition of ENaC. To that end, two-electrode voltage-clamp experiments were performed on Xenopus oocytes coexpressing ENaC together with CFTR, the multidrug resistance protein MDR1, the sulfonyl urea receptor SUR1, or the cadmium permease YCF1. Except for CFTR, none of the other ABC proteins were able to inhibit ENaC. Several truncated versions of CFTR were examined for their inhibitory effects on ENaC. In fact, it is shown that C-terminal truncated CFTR is able to inhibit ENaC on activation by intracellular cAMP. Moreover, the data also show that an intact first-nucleotide binding domain (NBF-1) is important for inhibition of ENaC. We conclude that NBF-1 of CFTR contains a CFTR-specific regulatory site that down-regulates ENaC. It is speculated that this regulatory site also is needed for CFTR-mediated interactions with other membrane proteins and that it is not present in NBF-1 of other ABC proteins.
Aguilar-Bryan,
Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.
1995, Pubmed
Aguilar-Bryan,
Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion.
1995,
Pubmed
Annereau,
A novel model for the first nucleotide binding domain of the cystic fibrosis transmembrane conductance regulator.
1997,
Pubmed
Boucher,
Evidence for reduced Cl- and increased Na+ permeability in cystic fibrosis human primary cell cultures.
1988,
Pubmed
Briel,
Cl- transport by cystic fibrosis transmembrane conductance regulator (CFTR) contributes to the inhibition of epithelial Na+ channels (ENaCs) in Xenopus oocytes co-expressing CFTR and ENaC.
1998,
Pubmed
,
Xenbase
Egan,
Defective regulation of outwardly rectifying Cl- channels by protein kinase A corrected by insertion of CFTR.
1992,
Pubmed
Gabriel,
CFTR and outward rectifying chloride channels are distinct proteins with a regulatory relationship.
1993,
Pubmed
Grubb,
Intestinal physiology and pathology in gene-targeted mouse models of cystic fibrosis.
1997,
Pubmed
Hipper,
Mutations in the putative pore-forming domain of CFTR do not change anion selectivity of the cAMP activated Cl- conductance.
1995,
Pubmed
,
Xenbase
Ishida-Takahashi,
Cystic fibrosis transmembrane conductance regulator mediates sulphonylurea block of the inwardly rectifying K+ channel Kir6.1.
1998,
Pubmed
Ismailov,
G-protein regulation of outwardly rectified epithelial chloride channels incorporated into planar bilayer membranes.
1996,
Pubmed
Jovov,
Cystic fibrosis transmembrane conductance regulator is required for protein kinase A activation of an outwardly rectified anion channel purified from bovine tracheal epithelia.
1995,
Pubmed
Jovov,
Interaction between cystic fibrosis transmembrane conductance regulator and outwardly rectified chloride channels.
1995,
Pubmed
Kunzelmann,
Inhibition of epithelial Na+ currents by intracellular domains of the cystic fibrosis transmembrane conductance regulator.
1997,
Pubmed
,
Xenbase
Kunzelmann,
Na+ and Cl- conductances in airway epithelial cells: increased Na+ conductance in cystic fibrosis.
1995,
Pubmed
Lorenz,
Heteromultimeric CLC chloride channels with novel properties.
1996,
Pubmed
,
Xenbase
Mall,
Wild type but not deltaF508 CFTR inhibits Na+ conductance when coexpressed in Xenopus oocytes.
1996,
Pubmed
,
Xenbase
Mall,
The amiloride-inhibitable Na+ conductance is reduced by the cystic fibrosis transmembrane conductance regulator in normal but not in cystic fibrosis airways.
1998,
Pubmed
Manavalan,
Sequence homologies between nucleotide binding regions of CFTR and G-proteins suggest structural and functional similarities.
1995,
Pubmed
McNicholas,
Sensitivity of a renal K+ channel (ROMK2) to the inhibitory sulfonylurea compound glibenclamide is enhanced by coexpression with the ATP-binding cassette transporter cystic fibrosis transmembrane regulator.
1996,
Pubmed
,
Xenbase
McNicholas,
A functional CFTR-NBF1 is required for ROMK2-CFTR interaction.
1997,
Pubmed
,
Xenbase
Orlando,
Colonic and esophageal transepithelial potential difference in cystic fibrosis.
1989,
Pubmed
Riordan,
The cystic fibrosis transmembrane conductance regulator.
1993,
Pubmed
Ruknudin,
Novel subunit composition of a renal epithelial KATP channel.
1998,
Pubmed
,
Xenbase
Schwiebert,
Both CFTR and outwardly rectifying chloride channels contribute to cAMP-stimulated whole cell chloride currents.
1994,
Pubmed
Schwiebert,
CFTR regulates outwardly rectifying chloride channels through an autocrine mechanism involving ATP.
1995,
Pubmed
Schwiebert,
Chloride channel and chloride conductance regulator domains of CFTR, the cystic fibrosis transmembrane conductance regulator.
1998,
Pubmed
,
Xenbase
Seibert,
cAMP-dependent protein kinase-mediated phosphorylation of cystic fibrosis transmembrane conductance regulator residue Ser-753 and its role in channel activation.
1995,
Pubmed
Short,
An apical PDZ protein anchors the cystic fibrosis transmembrane conductance regulator to the cytoskeleton.
1998,
Pubmed
Stutts,
Cystic fibrosis transmembrane conductance regulator inverts protein kinase A-mediated regulation of epithelial sodium channel single channel kinetics.
1997,
Pubmed
Tommasini,
The human multidrug resistance-associated protein functionally complements the yeast cadmium resistance factor 1.
1996,
Pubmed
Wang,
Peptide binding consensus of the NHE-RF-PDZ1 domain matches the C-terminal sequence of cystic fibrosis transmembrane conductance regulator (CFTR).
1998,
Pubmed
