ArticleGastroenterology2013
Irbit mediates synergy between ca(2+) and cAMP signaling pathways during epithelial transport in mice.
Article in Gastroenterology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 95 citations in OpenAlex.
- Review
- Pancreatitis: correcting CFTR expression and function as a promising effective treatment.Frontiers in physiology · 2026Review
- Beyond the mutations: spatiotemporal regulation of CFTR by cAMP and calcium signaling in epithelial physiology and cystic fibrosis.Cellular & molecular biology letters · 2025Review
- Lipid transporters E-Syt3 and ORP5 regulate epithelial ion transport by controlling phosphatidylserine enrichment at ER/PM junctions.The EMBO journal · 2025Article
- The function of chloride channels in digestive system disease (Review).International journal of molecular medicine · 2025Review
- Multiple cAMP/PKA complexes at the STIM1 ER/PM junction specified by E-Syt1 and E-Syt2 reciprocally gates ANO1 (TMEM16A) via CaNature communications · 2025Article
- AHCYL1 mediates the tumor-promoting effect of PREX2 in non-small cell lung carcinoma.Theranostics · 2025Article
- CFTR expression in human salivary gland acinar cells.American journal of physiology. Cell physiology · 2024Article
- SLC26 Anion Transporters.Handbook of experimental pharmacology · 2024Review
- The Role of Uroguanylin in Regulation of Ion Transport in Salivary Glands.Acta stomatologica Croatica · 2023Article
- SLC26A3 (DRA) is stimulated in a synergistic, intracellular CaAmerican journal of physiology. Cell physiology · 2023Article
- Synergistic effects of agonists and two-pore-domain potassium channels on secretory responses of human pancreatic duct cells Capan-1.Pflugers Archiv : European journal of physiology · 2023Article
- Dietary sodium enhances the expression of SLC4 family transporters, IRBIT, L-IRBIT, and PP1 in rat kidney: Insights into the molecular mechanism for renal sodium handling.Frontiers in physiology · 2023Article
- Impaired regulation of PMCA activity by defective CFTR expression promotes epithelial cell damage in alcoholic pancreatitis and hepatitis.Cellular and molecular life sciences : CMLS · 2022Article
- Synaptic plasticity in hippocampal CA1 neurons of mice lacking inositol-1,4,5-trisphosphate receptor-binding protein released with IPLearning & memory (Cold Spring Harbor, N.Y.) · 2022Article
- Review
- Combined agonists act synergistically to increase mucociliary clearance in a cystic fibrosis airway model.Scientific reports · 2021Article
- Endoplasmic Reticulum-Plasma Membrane Contact Sites as an Organizing Principle for Compartmentalized Calcium and cAMP Signaling.International journal of molecular sciences · 2021Review
- IRBIT activates NBCe1-B by releasing the auto-inhibition module from the transmembrane domain.The Journal of physiology · 2021Article
- Protective Role of IRBIT on Sodium Bicarbonate Cotransporter-n1 for Migratory Cancer Cells.Pharmaceutics · 2020Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 8 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsThe cyclic adenosine monophosphate (cAMP) and Ca(2+) signaling pathways synergize to regulate many physiological functions. However, little is known about the mechanisms by which these pathways interact. We investigated the synergy between these signaling pathways in mouse pancreatic and salivary gland ducts.
methodsWe created mice with disruptions in genes encoding the solute carrier family 26, member 6 (Slc26a6(-/-) mice) and inositol 1,4,5-triphosphate (InsP3) receptor-binding protein released with InsP3 (Irbit(-/-)) mice. We investigated fluid secretion by sealed pancreatic ducts and the function of Slc26a6 and the cystic fibrosis transmembrane conductance regulator (CFTR) in HeLa cells and in ducts isolated from mouse pancreatic and salivary glands. Slc26a6 activity was assayed by measuring intracellular pH, and CFTR activity was assayed by measuring Cl(-) current. Protein interactions were determined by immunoprecipitation analyses.
resultsIrbit mediated the synergistic activation of CFTR and Slc26a6 by Ca(2+) and cAMP. In resting cells, Irbit was sequestered by InsP3 receptors (IP3Rs) in the endoplasmic reticulum. Stimulation of Gs-coupled receptors led to phosphorylation of IP3Rs, which increased their affinity for InsP3 and reduced their affinity for Irbit. Subsequent weak stimulation of Gq-coupled receptors, which led to production of low levels of IP3, caused dissociation of Irbit from IP3Rs and allowed translocation of Irbit to CFTR and Slc26a6 in the plasma membrane. These processes stimulated epithelial secretion of electrolytes and fluid. These pathways were not observed in pancreatic and salivary glands from Irbit(-/-) or Slc26a6(-/-) mice, or in salivary gland ducts expressing mutant forms of IP3Rs that could not undergo protein kinase A-mediated phosphorylation.
conclusionsIrbit promotes synergy between the Ca(2+) and cAMP signaling pathways in cultured cells and in pancreatic and salivary ducts from mice. Defects in this pathway could be involved in cystic fibrosis, pancreatitis, or Sjögren syndrome.
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