ArticleThe Biochemical journal2011
Functional regulation of cystic fibrosis transmembrane conductance regulator-containing macromolecular complexes: a small-molecule inhibitor approach.
Article in The Biochemical journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Specificity in PDZ-peptide interaction networks: Computational analysis and review.Journal of structural biology: X · 2020Review
- An Intriguing Involvement of Mitochondria in Cystic Fibrosis.Journal of clinical medicine · 2019Review
- Emerging Themes in PDZ Domain Signaling: Structure, Function, and Inhibition.International review of cell and molecular biology · 2019Review
- Review
- Regulation of Transporters and Channels by Membrane-Trafficking Complexes in Epithelial Cells.Cold Spring Harbor perspectives in biology · 2017Review
- CFTR-NHERF2-LPA₂ Complex in the Airway and Gut Epithelia.International journal of molecular sciences · 2017Review
- Drug-induced secretory diarrhea: A role for CFTR.Pharmacological research · 2015Review
- Altered cGMP dynamics at the plasma membrane contribute to diarrhea in ulcerative colitis.The American journal of pathology · 2015Article
- Förster resonance energy transfer - an approach to visualize the spatiotemporal regulation of macromolecular complex formation and compartmentalized cell signaling.Biochimica et biophysica acta · 2014Review
- Small molecule inhibition of the Na(+)/H(+) exchange regulatory factor 1 and parathyroid hormone 1 receptor interaction.Biochemistry · 2014Article
- Structural insights into PDZ-mediated interaction of NHERF2 and LPA(2), a cellular event implicated in CFTR channel regulation.Biochemical and biophysical research communications · 2014Article
- CFTR activity and mitochondrial function.Redox biology · 2013Review
- CFTR-SLC26 transporter interactions in epithelia.Biophysical reviews · 2012Article
- Arsenic promotes ubiquitinylation and lysosomal degradation of cystic fibrosis transmembrane conductance regulator (CFTR) chloride channels in human airway epithelial cells.The Journal of biological chemistry · 2012Article
- Recent advances and new perspectives in targeting CFTR for therapy of cystic fibrosis and enterotoxin-induced secretory diarrheas.Future medicinal chemistry · 2012Review
- Functional Rescue of F508del-CFTR Using Small Molecule Correctors.Frontiers in pharmacology · 2012Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
CFTR (cystic fibrosis transmembrane conductance regulator) has been shown to form multiple protein macromolecular complexes with its interacting partners at discrete subcellular microdomains to modulate trafficking, transport and signalling in cells. Targeting protein-protein interactions within these macromolecular complexes would affect the expression or function of the CFTR channel. We specifically targeted the PDZ domain-based LPA2 (type 2 lysophosphatidic acid receptor)-NHERF2 (Na+/H+ exchanger regulatory factor-2) interaction within the CFTR-NHERF2-LPA2-containing macromolecular complexes in airway epithelia and tested its regulatory role on CFTR channel function. We identified a cell-permeable small-molecule compound that preferentially inhibits the LPA2-NHERF2 interaction. We show that this compound can disrupt the LPA2-NHERF2 interaction in cells and thus compromises the integrity of macromolecular complexes. Functionally, it elevates cAMP levels in proximity to CFTR and upregulates its channel activity. The results of the present study demonstrate that CFTR Cl- channel function can be finely tuned by modulating PDZ domain-based protein-protein interactions within the CFTR-containing macromolecular complexes. The present study might help to identify novel therapeutic targets to treat diseases associated with dysfunctional CFTR Cl- channels.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.