ArticleThe Journal of clinical investigation2009
Differential roles of NHERF1, NHERF2, and PDZK1 in regulating CFTR-mediated intestinal anion secretion in mice.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 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.
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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
56 citing papers in PubMed, 359 citations in OpenAlex.
- Regulation of CFTR stability at the plasma membrane-Mechanisms and therapeutic opportunities in cystic fibrosis.FEBS letters · 2026Review
- Sequence Engineering at Non-motif Modulator Residues Yields a Peptide That Effectively Targets a Single PDZ Protein in a Disease-relevant Cellular Context.Journal of molecular biology · 2026Article
- Nherf2 is a major determinant of bile acid pool dynamics and contributes to regulation of Western diet-induced obesity.American journal of physiology. Cell physiology · 2025Article
- Sequence engineering at non-motif modulator residues yields a peptide that effectively targets a single PDZ protein in a disease-relevant cellular context.bioRxiv : the preprint server for biology · 2025Article
- NHERF2 as a Novel Biomarker for Distinguishing MAC Pulmonary Disease from Tuberculosis Based on Proteome Analysis of Serum Extracellular Vesicles.International journal of molecular sciences · 2025Article
- MRTF-A gain-of-function in mice impairs homeostatic renewal of the intestinal epithelium.Cell death & disease · 2023Article
- It Takes Two to Tango! Protein-Protein Interactions behind cAMP-Mediated CFTR Regulation.International journal of molecular sciences · 2023Review
- Polarized transport of membrane and secreted proteins during lumen morphogenesis.Seminars in cell & developmental biology · 2023Review
- Application of the steady-state intestinal perfusion system in measuring intestinal fluid absorption and bicarbonate secretionFrontiers in physiology · 2023Article
- Compensatory Upregulation of LPACells · 2022Article
- Functional role and regulation of permeability-glycoprotein (P-gp) in the fetal membrane during drug transportation.American journal of reproductive immunology (New York, N.Y. : 1989) · 2022Article
- Self-organization of apical membrane protein sorting in epithelial cells.The FEBS journal · 2022Article
- The β2-adrenergic receptor in the apical membrane of intestinal enterocytes senses sugars to stimulate glucose uptake from the gut.Frontiers in cell and developmental biology · 2022Article
- Lack of CFTR alters the ferret pancreatic ductal epithelial secretome and cellular proteome: Implications for exocrine/endocrine signaling.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2022Article
- Article
- Lysophosphatidic Acid Increases Maturation of Brush Borders and SGLT1 Activity in MYO5B-deficient Mice, a Model of Microvillus Inclusion Disease.Gastroenterology · 2020Article
- MotifAnalyzer-PDZ: A computational program to investigate the evolution of PDZ-binding target specificity.Protein science : a publication of the Protein Society · 2019Article
- Expression of lysophosphatidic acid receptor 5 is necessary for the regulation of intestinal NaAmerican journal of physiology. Gastrointestinal and liver physiology · 2018Article
- Prevention and treatment of secretory diarrhea by the lysophosphatidic acid analog Rx100.Experimental biology and medicine (Maywood, N.J.) · 2018Article
- CFTR-NHERF2-LPA₂ Complex in the Airway and Gut Epithelia.International journal of molecular sciences · 2017Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
The epithelial anion channel CFTR interacts with multiple PDZ domain-containing proteins. Heterologous expression studies have demonstrated that the Na+/H+ exchanger regulatory factors, NHERF1, NHERF2, and PDZK1 (NHERF3), modulate CFTR membrane retention, conductivity, and interactions with other transporters. To study their biological roles in vivo, we investigated CFTR-dependent duodenal HCO3- secretion in mouse models of Nherf1, Nherf2, and Pdzk1 loss of function. We found that Nherf1 ablation strongly reduced basal as well as forskolin-stimulated (FSK-stimulated) HCO3- secretory rates and blocked beta2-adrenergic receptor (beta2-AR) stimulation. Conversely, Nherf2-/- mice displayed augmented FSK-stimulated HCO3- secretion. Furthermore, although lysophosphatidic acid (LPA) inhibited FSK-stimulated HCO3- secretion in WT mice, this effect was lost in Nherf2-/- mice. Pdzk1 ablation reduced basal, but not FSK-stimulated, HCO3- secretion. In addition, laser microdissection and quantitative PCR revealed that the beta2-AR and the type 2 LPA receptor were expressed together with CFTR in duodenal crypts and that colocalization of the beta2-AR and CFTR was reduced in the Nherf1-/- mice. These data suggest that the NHERF proteins differentially modulate duodenal HCO3- secretion: while NHERF1 is an obligatory linker for beta2-AR stimulation of CFTR, NHERF2 confers inhibitory signals by coupling the LPA receptor to CFTR.
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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.