| Claudin-8 expression in renal epithelial cells augments the paracellular barrier by replacing endogenous claudin-2. | |
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MedLine Citation:
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PMID: 17516019 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Claudins are transmembrane proteins of the tight junction that determine and regulate paracellular ion permeability. We previously reported that claudin-8 reduces paracellular cation permeability when expressed in low-resistance Madin-Darby canine kidney (MDCK) II cells. Here, we address how the interaction of heterologously expressed claudin-8 with endogenous claudin isoforms impacts epithelial barrier properties. In MDCK II cells, barrier improvement by claudin-8 is accompanied by a reduction of endogenous claudin-2 protein at the tight junction. Here, we show that this is not because of relocalization of claudin-2 into the cytosolic pool but primarily due to a decrease in gene expression. Claudin-8 also affects the trafficking of claudin-2, which was displaced specifically from the junctions at which claudin-8 was inserted. To test whether replacement of cation-permeable claudin-2 mediates the effect of claudin-8 on the electrophysiological phenotype of the host cell line, we expressed claudin-8 in high-resistance MDCK I cells, which lack endogenous claudin-2. Unlike in MDCK II cells, induction of claudin-8 in MDCK I cells (which did not affect levels of endogenous claudins) did not alter paracellular ion permeability. Furthermore, when endogenous claudin-2 in MDCK II cells was downregulated by epidermal growth factor to create a cell model with low transepithelial resistance and low levels of claudin-2, the permeability effects of claudin-8 were also abolished. Our findings demonstrate that claudin overexpression studies measure the combined effect of alterations in both endogenous and exogenous claudins, thus explaining the dependence of the phenotype on the host cell line. |
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Authors:
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Susanne Angelow; Eveline E Schneeberger; Alan S L Yu |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2007-05-22 |
Journal Detail:
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Title: The Journal of membrane biology Volume: 215 ISSN: 0022-2631 ISO Abbreviation: J. Membr. Biol. Publication Date: 2007 Feb |
Date Detail:
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Created Date: 2007-08-17 Completed Date: 2007-11-19 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0211301 Medline TA: J Membr Biol Country: United States |
Other Details:
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Languages: eng Pagination: 147-59 Citation Subset: IM |
Affiliation:
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Division of Nephrology, Department of Medicine, University of Southern California Keck School of Medicine, 2025 Zonal Avenue, Los Angeles, CA 90033, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Northern Cell Line Dogs Epidermal Growth Factor / pharmacology Epithelial Cells / drug effects, metabolism* Gene Expression / drug effects Immunoblotting Immunohistochemistry Kidney / drug effects, metabolism Membrane Proteins / genetics, metabolism*, physiology Mice Tight Junctions / drug effects, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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DK 062283/DK/NIDDK NIH HHS; DK 48522/DK/NIDDK NIH HHS; HL 25822/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Membrane Proteins; 0/claudin 8; 62229-50-9/Epidermal Growth Factor |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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