ArticleAmerican journal of physiology. Renal physiology2010
Nedd4-2 interacts with occludin to inhibit tight junction formation and enhance paracellular conductance in collecting duct epithelia.
Article in American journal of physiology. Renal physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Identification of E3 ligase substrates and PROTAC-induced ubiquitylation sites using proximity-based identification of ubiquitin sites (PrIUS).Communications biology · 2026Article
- HSV-1 UL56 protein recruits cellular NEDD4-family ubiquitin ligases to suppress CD1d expression and NKT cell function.Journal of virology · 2025Article
- The Basic Requirement of Tight Junction Proteins in Blood-Brain Barrier Function and Their Role in Pathologies.International journal of molecular sciences · 2024Review
- Article
- Review
- Post-Translational Modifications in Atopic Dermatitis: Current Research and Clinical Relevance.Frontiers in cell and developmental biology · 2022Review
- The role of ubiquitination and deubiquitination in the regulation of cell junctions.Protein & cell · 2018Review
- Proteomic and cellular localisation studies suggest non-tight junction cytoplasmic and nuclear roles for occludin in astrocytes.The European journal of neuroscience · 2018Article
- Dual catenin loss in murine liver causes tight junctional deregulation and progressive intrahepatic cholestasis.Hepatology (Baltimore, Md.) · 2018Article
- The Role of Intercalated CellJournal of the American Society of Nephrology : JASN · 2018Article
- Disruption of the epithelial barrier during intestinal inflammation: Quest for new molecules and mechanisms.Biochimica et biophysica acta. Molecular cell research · 2017Review
- Data integration in physiology using Bayes' rule and minimum Bayes' factors: deubiquitylating enzymes in the renal collecting duct.Physiological genomics · 2017Article
- Review
- Article
- Regulation of transport in the connecting tubule and cortical collecting duct.Comprehensive Physiology · 2012Review
- Occludin: one protein, many forms.Molecular and cellular biology · 2012Review
- Article
- Occludin regulation of blood-brain barrier and potential therapeutic target in ischemic stroke.Brain circulationReview
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Authors and funding
3 authors.
Funding
Abstract
Nedd4-2, a E3 ubiquitin ligase, regulates epithelial sodium channel-mediated transcellular Na(+) transport in the collecting duct. We investigated the effect of Nedd4-2 on the junctional complex and paracellular conductance in mpkCCD(c14) cells, a collecting duct cell line. We demonstrate that Nedd4-2 coimmunoprecipitated with and reduced the expression of transfected occludin in HEK293 cells. This interaction was mediated via a conserved PY motif in the COOH terminus of occludin and mutation of this PY motif increased the half-life of transfected occludin in HEK293 cells from 6.4 to 11.4 h. We demonstrate that Nedd4-2 ubiquitinates occludin, which was not seen when a catalytically inactive form of Nedd4-2 was used. Overexpression of Nedd4-2 in mpkCCD(c14) cells reduced occludin at the tight junction and transiently increased paracellular conductance in a Ca(2+) switch assay consistent with a delay in the formation of tight junctions. Conversely, siRNA-mediated knockdown of Nedd4-2 increased occludin levels and reduced paracellular conductance. In summary, we demonstrate that Nedd4-2 plays a role in tight junction assembly and the regulation of paracellular conductance in the collecting duct.
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Registered trials
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