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Cited by 1,151Barrier Structure and Function StudiesCell Adhesion Molecules ResearchIon Transport and Channel Regulation

Direct Binding of Three Tight Junction-Associated Maguks, Zo-1, Zo-2, and Zo-3, with the Cooh Termini of Claudins

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Itoh, Masahiko, Furuse, Mikio, Morita, Kazumasa, Kubota, Koji, Saitou, Mitinori, Tsukita, Shoichiro·1999·The Journal of Cell Biology
DOI 10.1083/jcb.147.6.1351PMC PMC2168087
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Abstract

ZO-1, ZO-2, and ZO-3, which contain three PDZ domains (PDZ1 to -3), are concentrated at tight junctions (TJs) in epithelial cells. TJ strands are mainly composed of two distinct types of four-transmembrane proteins, occludin, and claudins, between which occludin was reported to directly bind to ZO-1/ZO-2/ZO-3. However, in occludin-deficient intestinal epithelial cells, ZO-1/ZO-2/ZO-3 were still recruited to TJs. We then examined the possible interactions between ZO-1/ZO-2/ZO-3 and claudins. ZO-1, ZO-2, and ZO-3 bound to the COOH-terminal YV sequence of claudin-1 to -8 through their PDZ1 domains in vitro. Then, claudin-1 or -2 was transfected into L fibroblasts, which express ZO-1 but not ZO-2 or ZO-3. Claudin-1 and -2 were concentrated at cell–cell borders in an elaborate network pattern, to which endogenous ZO-1 was recruited. When ZO-2 or ZO-3 were further transfected, both were recruited to the claudin-based networks together with endogenous ZO-1. Detailed analyses showed that ZO-2 and ZO-3 are recruited to the claudin-based networks through PDZ2 (ZO-2 or ZO-3)/PDZ2 (endogenous ZO-1) and PDZ1 (ZO-2 or ZO-3)/COOH-terminal YV (claudins) interactions. In good agreement, PDZ1 and PDZ2 domains of ZO-1/ZO-2/ZO-3 were also recruited to claudin-based TJs, when introduced into cultured epithelial cells. The possible molecular architecture of TJ plaque structures is discussed.

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  • ZO-1 interacts with the C-terminus of all claudins and occludin.

    “However, such a model does not explain why specifically claudin-1, but not claudin-4 or occludin, is lacking from the granular layer whereas ZO-1 interacts with the C-terminus of all claudins and occludin (Fanning et al, 1998;Itoh et al, 1999).”

    From E‐cadherin is essential for in vivo epidermal barrier function by regulating tight junctions (2005) · cites this paper as Itoh et al, 1999

    The Results (page unavailable) show that ZO-1 binds the C-terminal regions of claudin-1 through claudin-8, which includes claudin-1 and claudin-4. The paper also reports binding between ZO-1 and the C-terminal tail of occludin. But it describes at least 16 claudin family members and does not establish binding to all of them. (LLM, conf=0.89)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Itoh, M., Furuse, M., Morita, K., Kubota, K., Saitou, M., & Tsukita, S.
Affiliations
  • Kyoto University (JP)
  • aDepartment of Cell Biology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan
ORCID
Venue
The Journal of Cell Biology
Publisher
Rockefeller University Press
Published
1999-12-13
Volume
147
Issue
6
Pages
1351-1363
ISSN
  • 0021-9525 (ISSN-L)
  • 1540-8140
DOI
10.1083/jcb.147.6.1351
PMC
PMC2168087
OpenAlex
W2040509610
Cited by
1,151
References
3
Citations by year
2026: 17 · 2025: 18 · 2024: 37 · 2023: 35 · 2022: 44 · 2021: 50 · 2020: 44 · 2019: 40 · 2018: 41 · 2017: 42 · 2016: 32 · 2015: 37 · 2014: 34 · 2013: 47 · 2012: 53
FWCI
22.59
Type
journal article
Language
en
Open access
Locations
  • The Journal of Cell Biology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Keywords
tight junctions, ZO-1, ZO-2, ZO-3, claudins, claudin-1, claudin-2, PDZ domain, protein-protein interaction, occludin, epithelial cells
MeSH terms
Amino Acid Sequence, Animals, Carrier Proteins, Cells, Cultured, Epithelial Cells, Intestines, L Cells, Membrane Proteins, Models, Biological, Phosphoproteins, Protein Binding, Recombinant Fusion Proteins, Transfection, Gene Deletion, Mice, Knockout, Tight Junctions, Amino Acid Motifs, Mice, Claudins, Claudin-1, Occludin, Zonula Occludens Proteins, Zonula Occludens-1 Protein, Zonula Occludens-2 Protein

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