ArticleThe Journal of general physiology2004
Inhibition and redistribution of NHE3, the apical Na+/H+ exchanger, by Clostridium difficile toxin B.
Article in The Journal of general physiology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed, 72 citations in OpenAlex.
- Ecological and dietary strategies to constrain Clostridioides difficile.Cell host & microbe · 2026Review
- Diet-Microbiota-Host Interactions in Regulation of Cardiometabolic Homeostasis: Emerging Mechanisms and Therapeutic Potential.Microbiota and host · 2025Article
- Breaking Down Barriers: Epithelial Contributors to Monogenic IBD Pathogenesis.Inflammatory bowel diseases · 2024Review
- New functions and roles of the NaPflugers Archiv : European journal of physiology · 2024Review
- Streptolysin S targets the sodium-bicarbonate cotransporter NBCn1 to induce inflammation and cytotoxicity in human keratinocytes during Group A Streptococcal infection.Frontiers in cellular and infection microbiology · 2022Article
- Intestine-Specific NHE3 Deletion in Adulthood Causes Microbial Dysbiosis.Frontiers in cellular and infection microbiology · 2022Article
- The Role of Plasma Membrane Sodium/Hydrogen Exchangers in Gastrointestinal Functions: Proliferation and Differentiation, Fluid/Electrolyte Transport and Barrier Integrity.Frontiers in physiology · 2022Review
- Rho GTPases in kidney physiology and diseases.Small GTPases · 2022Article
- Article
- The therapeutic importance of acid-base balance.Biochemical pharmacology · 2021Review
- Research in a time of enteroids and organoids: how the human gut model has transformed the study of enteric bacterial pathogens.Gut microbes · 2020Review
- Pharmacological reversal of renal cysts from secretion to absorption suggests a potential therapeutic strategy for managing autosomal dominant polycystic kidney disease.The Journal of biological chemistry · 2019Article
- Druggable targets in the Rho pathway and their promise for therapeutic control of blood pressure.Pharmacology & therapeutics · 2019Review
- (Patho-)Physiology of NaFrontiers in physiology · 2019Review
- Faecalibacterium prausnitzii and a Prebiotic Protect Intestinal Health in a Mouse Model of Antibiotic and Clostridium difficile Exposure.JPEN. Journal of parenteral and enteral nutrition · 2018Article
- Microbial dysbiosis associated with impaired intestinal NaMucosal immunology · 2018Article
- Clostridium difficile toxins A and B decrease intestinal SLC26A3 protein expression.American journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Pathophysiology of avian intestinal ion transport.World's poultry science journal · 2018Article
- Antidiarrheal Action ofFrontiers in microbiology · 2018Article
- The Role of Ion Transporters in the Pathophysiology of Infectious Diarrhea.Cellular and molecular gastroenterology and hepatology · 2018Review
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
NHE3, the apical isoform of the Na(+)/H(+) exchanger, is central to the absorption of salt and water across the intestinal epithelium. We report that treatment of epithelial cells with toxin B of Clostridium difficile, a diarrheal pathogen, causes a pronounced inhibition of NHE3 activity, with little effect on the basolateral NHE1 isoform. Depression of NHE3 activity is accompanied by the translocation of apical exchangers to a subapical endomembrane compartment. Treatment of cells with toxin B increased the fraction of exchangers that were solubilized by nonionic detergents and induced dephosphorylation and extensive redistribution of ezrin. The Rho-kinase inhibitor, Y-27632, also altered the distribution and activity of NHE3. We suggest that inactivation of Rho-family GTPases by clostridial toxin B alters the interaction between NHE3 and the microvillar cytoskeleton, possibly by impairing the ability of ezrin to bridge the exchangers to filamentous actin. Detachment of NHE3 from the actin skeleton would facilitate its internalization, resulting in net disappearance from the apical surface. The consequent inhibition of transport is likely to contribute to the diarrheal effects of C. difficile.
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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.