ArticleCell2007
Spatiotemporal coupling of cAMP transporter to CFTR chloride channel function in the gut epithelia.
Article in Cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
114 citing papers in PubMed, 205 citations in OpenAlex.
- Mechanistic Insights Into the Anti-Constipation Potential of Xiaogan Jianwei Formula: Integration of HPLC-Q-TOF MS/MS, Network Pharmacology, In Vivo Validation, and Gut Microbiota.Biomedical chromatography : BMC · 2026Article
- Regulation of CFTR stability at the plasma membrane-Mechanisms and therapeutic opportunities in cystic fibrosis.FEBS letters · 2026Review
- Effects of cAMP and CFTR modulation on apical fluid pH in human airway Calu-3 cells.Physiological reports · 2026Article
- Beyond the mutations: spatiotemporal regulation of CFTR by cAMP and calcium signaling in epithelial physiology and cystic fibrosis.Cellular & molecular biology letters · 2025Review
- Protein Kinase A and assembly of an ABCC4 protein network.Nature communications · 2025Article
- EMC3 is critical for CFTR function and calcium mobilization in the mouse intestinal epithelium.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Oligomerization of drug transporters: Forms, functions, and mechanisms.Acta pharmaceutica Sinica. B · 2024Review
- Structural basis of prostaglandin efflux by MRP4.Nature structural & molecular biology · 2024Article
- Functional Consequences of CFTR Interactions in Cystic Fibrosis.International journal of molecular sciences · 2024Review
- Comparing ATPase activity of ATP-binding cassette subfamily C member 4, lamprey CFTR, and human CFTR using an antimony-phosphomolybdate assay.Frontiers in pharmacology · 2024Article
- SMYD2 regulates vascular smooth muscle cell phenotypic switching and intimal hyperplasia via interaction with myocardin.Cellular and molecular life sciences : CMLS · 2023Article
- It Takes Two to Tango! Protein-Protein Interactions behind cAMP-Mediated CFTR Regulation.International journal of molecular sciences · 2023Review
- Deafness-Associated ADGRV1 Mutation Impairs USH2A Stability through Improper Phosphorylation of WHRN and WDSUB1 Recruitment.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Structural basis for substrate and inhibitor recognition of human multidrug transporter MRP4.Communications biology · 2023Article
- SMYD2 Regulates Vascular Smooth Muscle Cell Phenotypic Switching and Intimal Hyperplasia via Interaction with Myocardin.Research square · 2023Article
- A conserved WXXE motif is an apical delivery determinant of ABC transporter C subfamily isoforms.Cell structure and function · 2023Article
- Article
- Guanylate cyclase-C agonists as peripherally acting treatments of chronic visceral pain.Trends in pharmacological sciences · 2022Review
- Potentiation of long-acting βRespiratory research · 2021Article
- A SNARE protein Syntaxin 17 captures CFTR to potentiate autophagosomal clearance under stress.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
54 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 3 countries.
Funding
Abstract
Cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride channel localized at apical cell membranes and exists in macromolecular complexes with a variety of signaling and transporter molecules. Here, we report that the multidrug resistance protein 4 (MRP4), a cAMP transporter, functionally and physically associates with CFTR. Adenosine-stimulated CFTR-mediated chloride currents are potentiated by MRP4 inhibition, and this potentiation is directly coupled to attenuated cAMP efflux through the apical cAMP transporter. CFTR single-channel recordings and FRET-based intracellular cAMP dynamics suggest that a compartmentalized coupling of cAMP transporter and CFTR occurs via the PDZ scaffolding protein, PDZK1, forming a macromolecular complex at apical surfaces of gut epithelia. Disrupting this complex abrogates the functional coupling of cAMP transporter activity to CFTR function. Mrp4 knockout mice are more prone to CFTR-mediated secretory diarrhea. Our findings have important implications for disorders such as inflammatory bowel disease and secretory diarrhea.
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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.