ArticleThe Journal of biological chemistry2010
NHERF-1 binds to Mrp2 and regulates hepatic Mrp2 expression and function.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 56 citations in OpenAlex.
- A conserved WXXE motif is an apical delivery determinant of ABC transporter C subfamily isoforms.Cell structure and function · 2023Article
- NHERF1/EBP50 as a Target for Modulation of MRP Function in HepG2 Cells.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Molecular Regulation of Canalicular ABC Transporters.International journal of molecular sciences · 2021Review
- Neurotensin contributes to pediatric intestinal failure-associated liver disease via regulating intestinal bile acids uptake.EBioMedicine · 2018Article
- Circadian clock component PERIOD2 regulates diurnal expression of NaScientific reports · 2018Article
- Beyond Competitive Inhibition: Regulation of ABC Transporters by Kinases and Protein-Protein Interactions as Potential Mechanisms of Drug-Drug Interactions.Drug metabolism and disposition: the biological fate of chemicals · 2018Review
- Mechanisms of bile acid mediated inflammation in the liver.Molecular aspects of medicine · 2017Review
- CFTR-associated ligand is a negative regulator of Mrp2 expression.American journal of physiology. Cell physiology · 2017Article
- Proteomic analysis of imatinib-resistant CML-T1 cells reveals calcium homeostasis as a potential therapeutic target.Oncology reports · 2016Article
- Analysis of the Bile Salt Export Pump (ABCB11) Interactome Employing Complementary Approaches.PloS one · 2016Article
- Article
- Na(+) /H(+) exchanger regulatory factor 1 knockout mice have an attenuated hepatic inflammatory response and are protected from cholestatic liver injury.Hepatology (Baltimore, Md.) · 2015Article
- Structural and functional hepatocyte polarity and liver disease.Journal of hepatology · 2015Review
- Drug Transporters and Na+/H+ Exchange Regulatory Factor PSD-95/Drosophila Discs Large/ZO-1 Proteins.Pharmacological reviews · 2015Review
- Ezrin finds its groove in cholangiocytes.Hepatology (Baltimore, Md.) · 2015Article
- Role of protein kinase C isoforms in bile formation and cholestasis.Hepatology (Baltimore, Md.) · 2014Review
- Deleterious effect of oltipraz on extrahepatic cholestasis in bile duct-ligated mice.Journal of hepatology · 2014Article
- Taurolithocholate-induced MRP2 retrieval involves MARCKS phosphorylation by protein kinase Cϵ in HUH-NTCP Cells.Hepatology (Baltimore, Md.) · 2013Article
- Bile formation and secretion.Comprehensive Physiology · 2013Review
- EBP50 promotes focal adhesion turnover and vascular smooth muscle cells migration.Journal of molecular and cellular cardiology · 2012Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Multidrug resistance-associated protein 2 (Mrp2, Abcc2) is an ATP-binding cassette transporter localized at the canalicular membrane of hepatocytes that plays an important role in bile formation and detoxification. Prior in vitro studies suggest that Mrp2 can bind to Na(+)/H(+) exchanger regulatory factor 1 (NHERF-1), a PDZ protein that cross-links membrane proteins to actin filaments. However the role of NHERF-1 in the expression and functional regulation of Mrp2 remains largely unknown. Here we examine the interaction of Mrp2 and NHERF-1 and its physiological significance in HEK293 cells and NHERF-1 knock-out mice. Mrp2 co-precipitated with NHERF-1 in co-transfected HEK293 cells, an interaction that required the PDZ-binding motif of Mrp2. In NHERF-1(-/-) mouse liver, Mrp2 mRNA was unchanged but Mrp2 protein was reduced in whole cell lysates and membrane-enriched fractions to approximately 50% (p < 1 x 10(-6)) and approximately 70% (p < 0.05), respectively, compared with wild-type mice, suggesting that the down-regulation of Mrp2 expression was caused by post-transcriptional events. Mrp2 remained localized at the apical/canalicular membrane of NHERF-1(-/-) mouse hepatocytes, although its immunofluorescent labeling was noticeably weaker. Bile flow in NHERF-1(-/-) mice was reduced to approximately 70% (p < 0.001) in association with a 50% reduction in glutathione excretion (p < 0.05) and a 60% reduction in glutathione-methylfluorescein (GS-MF) excretion in isolated mouse hepatocyte (p < 0.01). Bile acid and bilirubin excretion remained unchanged compared with wild-type mice. These findings strongly suggest that NHERF-1 binds to Mrp2, and plays a critical role in the canalicular expression of Mrp2 and its function as a determinant of glutathione-dependent, bile acid-independent bile flow.
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