ArticleThe Journal of general physiology2005
CFTR gating I: Characterization of the ATP-dependent gating of a phosphorylation-independent CFTR channel (DeltaR-CFTR).
Article in The Journal of general physiology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 56 citations in OpenAlex.
- CFTR Modulators: From Mechanism to Targeted Therapeutics.Handbook of experimental pharmacology · 2024Article
- Functional stability of CFTR depends on tight binding of ATP at its degenerate ATP-binding site.The Journal of physiology · 2021Article
- Identification of binding sites for ivacaftor on the cystic fibrosis transmembrane conductance regulator.iScience · 2021Article
- Clinical and molecular characterization of the R751L-CFTR mutation.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Protein kinase A phosphorylation potentiates cystic fibrosis transmembrane conductance regulator gating by relieving autoinhibition on the stimulatory C terminus of the regulatory domain.The Journal of biological chemistry · 2020Article
- Identifying the molecular target sites for CFTR potentiators GLPG1837 and VX-770.The Journal of general physiology · 2019Article
- Ligand binding to a remote site thermodynamically corrects the F508del mutation in the human cystic fibrosis transmembrane conductance regulator.The Journal of biological chemistry · 2018Article
- Functional characterization reveals that zebrafish CFTR prefers to occupy closed channel conformations.PloS one · 2018Article
- Epithelial transport inThe Journal of general physiology · 2017Review
- Asymmetry of movements in CFTR's two ATP sites during pore opening serves their distinct functions.eLife · 2017Article
- The gating of the CFTR channel.Cellular and molecular life sciences : CMLS · 2017Review
- On the mechanism of gating defects caused by the R117H mutation in cystic fibrosis transmembrane conductance regulator.The Journal of physiology · 2016Article
- The cystic fibrosis transmembrane conductance regulator is an extracellular chloride sensor.Pflugers Archiv : European journal of physiology · 2015Article
- Mutating the Conserved Q-loop Glutamine 1291 Selectively Disrupts Adenylate Kinase-dependent Channel Gating of the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Reduces Channel Function in Primary Human Airway Epithelia.The Journal of biological chemistry · 2015Article
- Modulation of CFTR gating by permeant ions.The Journal of general physiology · 2015Article
- A single amino acid substitution in CFTR converts ATP to an inhibitory ligand.The Journal of general physiology · 2014Article
- Vx-770 potentiates CFTR function by promoting decoupling between the gating cycle and ATP hydrolysis cycle.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- The CFTR ion channel: gating, regulation, and anion permeation.Cold Spring Harbor perspectives in medicine · 2013Article
- Locating a plausible binding site for an open-channel blocker, GlyH-101, in the pore of the cystic fibrosis transmembrane conductance regulator.Molecular pharmacology · 2012Article
- Nonequilibrium gating of CFTR on an equilibrium theme.Physiology (Bethesda, Md.) · 2012Review
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
The CFTR chloride channel is activated by phosphorylation of serine residues in the regulatory (R) domain and then gated by ATP binding and hydrolysis at the nucleotide binding domains (NBDs). Studies of the ATP-dependent gating process in excised inside-out patches are very often hampered by channel rundown partly caused by membrane-associated phosphatases. Since the severed DeltaR-CFTR, whose R domain is completely removed, can bypass the phosphorylation-dependent regulation, this mutant channel might be a useful tool to explore the gating mechanisms of CFTR. To this end, we investigated the regulation and gating of the DeltaR-CFTR expressed in Chinese hamster ovary cells. In the cell-attached mode, basal DeltaR-CFTR currents were always obtained in the absence of cAMP agonists. Application of cAMP agonists or PMA, a PKC activator, failed to affect the activity, indicating that the activity of DeltaR-CFTR channels is indeed phosphorylation independent. Consistent with this conclusion, in excised inside-out patches, application of the catalytic subunit of PKA did not affect ATP-induced currents. Similarities of ATP-dependent gating between wild type and DeltaR-CFTR make this phosphorylation-independent mutant a useful system to explore more extensively the gating mechanisms of CFTR. Using the DeltaR-CFTR construct, we studied the inhibitory effect of ADP on CFTR gating. The Ki for ADP increases as the [ATP] is increased, suggesting a competitive mechanism of inhibition. Single channel kinetic analysis reveals a new closed state in the presence of ADP, consistent with a kinetic mechanism by which ADP binds at the same site as ATP for channel opening. Moreover, we found that the open time of the channel is shortened by as much as 54% in the presence of ADP. This unexpected result suggests another ADP binding site that modulates channel closing.
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