Claudin-1 contributes to the epithelial barrier function in MDCK cells
Abstract
Tight junctions (TJs) create a paracellular permeability barrier and also act as a fence preventing intermixing of proteins and lipids between the apical and basolateral plasma membranes. Recently, claudin-1 has been identified as an integral membrane protein localizing at TJs, and introduced claudin-1 can form TJ-like networks in fibroblasts. To investigate the function of claudin-1, MDCK cells were transfected with a mammalian expression vector containing myc-tagged mouse claudin-1, and four stable clones were obtained. The myc-tagged claudin-1 precisely colocalized with both occludin and ZO-1 at cell-cell contact sites, indicating that exogenous claudin-1 was properly targeted to the TJs. Immunoblot analysis revealed that overexpression of claudin-1 increased expression of ZO-1 but not of occludin or ZO-2. The barrier functions of these cells were evaluated by transepithelial electrical resistance (TER) and paracellular flux. Claudin-1-expressing cells exhibited about four times higher TER than wild-type MDCK cells. Consistent with the increase of TER, the cells overexpressing claudin-1 showed reduced paracellular flux, estimated at 4 and 40 kD FITC-dextrans. These results suggest that claudin-1 is involved in the barrier function at TJs.
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The size and ion selectivity of tight junctions depends on the type and levels of expression of claudins.
“The size and ion selectivity of tight junctions is variable within different tissues and depends on the type and levels of expression of claudins, four span transmembrane molecules, which constitute the tight junctional paired strands (Inai et al, 1999;Colegio et al, 2003).”
From E‐cadherin is essential for in vivo epidermal barrier function by regulating tight junctions (2005) · cites this paper as Inai et al, 1999
Overexpression of claudin-1 in MDCK cells results in a four-fold increase in transepidermal resistance.
“For example, overexpression of claudin-1 in MDCK cells results in a four-fold increase in transepidermal resistance, a measure of ion permeability (Inai et al, 1999).”
From E‐cadherin is essential for in vivo epidermal barrier function by regulating tight junctions (2005) · cites this paper as Inai et al, 1999
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Structure, function, and regulation of cellular tight junctions
Schneeberger, E. E., & Lynch, R. D. (1992) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.1992.262.6.l647 · Cited by 518 · see citing works
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Physiology and function of the tight junction
Anderson, J. M., & Van Itallie, C. M. (2009) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a002584 · Cited by 1,059 · see citing works
E‐cadherin is essential for in vivo epidermal barrier function by regulating tight junctions
Tunggal, J. A., Helfrich, I., Schmitz, A., Schwarz, H., Günzel, D., Fromm, M., Kemler, R., Krieg, T., & Niessen, C. M. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600605 · Cited by 491 · see citing works
The Blood-Retina Barrier: Tight Junctions and Barrier Modulation
Campbell, M., & Humphries, P. (2013) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4614-4711-5_3 · Cited by 270 · see citing works
Steelant, B., Seys, S. F., Boeckxstaens, G., Akdis, C. A., Ceuppens, J. L., & Hellings, P. W. (2017) · Rhinology journal · doi:10.4193/rhin15.376 · Cited by 47 · see citing works
- Authors
- Inai, T., Kobayashi, J., & Shibata, Y.
- Affiliations
- Kyushu University (JP)
- Corresponding author
- Inai, Tetsuichiro
- ORCID
- Inai, Tetsuichiro
- Venue
- European Journal of Cell Biology
- Publisher
- Elsevier BV
- Published
- 1999-12
- Volume
- 78
- Issue
- 12
- Pages
- 849-855
- ISSN
- 0171-9335 (ISSN-L)
- OpenAlex
- W2060986062
- Cited by
- 285
- References
- 1
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 11 · 2023: 7 · 2022: 11 · 2021: 8 · 2020: 17 · 2019: 10 · 2018: 14 · 2017: 11 · 2016: 16 · 2015: 10 · 2014: 14 · 2013: 10 · 2012: 10
- FWCI
- 4.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (08770015,09770010, 11770008)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- claudin-1, tight junctions, epithelial barrier function, MDCK cells, transepithelial electrical resistance, paracellular permeability, occludin, ZO-1, ZO-2, FITC-dextran
- MeSH terms
- Animals, Biological Transport, Cell Communication, Cell Line, Cell Membrane Permeability, Dogs, Epithelial Cells, Membrane Proteins, Tight Junctions, Mice, Claudin-1
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