Functional landscape of mechanistic diversity in 27 claudin family members at tight junctions

The diversity of epithelial paracellular barriers, essential for various biological functions, is primarily determined by the combination of 27 claudins (Cldns) that form tight junctions (TJs). However, the basis of their functional diversity remains largely unexplored. Here, we generated complete <i>Cldn</i>-null mouse epithelial cells to reconstitute the TJ paracellular barrier (TJ barrier) with individual Cldns. Each Cldn establishes its respective TJ barrier, either autonomously or nonautonomously, exhibiting distinct ion conductivity and selectivity. Clustering algorithms revealed a previously unidentified classification of Cldns into four main classes with well-defined subclasses, moving beyond the conventional paracellular barrier-versus-channel-forming dichotomy. Our findings, including the in vivo Cldn dynamics, provide a framework for understanding TJ barrier diversity and plasticity, offering insights into organ-specific homeostasis and guiding therapeutic strategies targeting TJ barriers in health and disease.

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Publication Details

Journal
Science Advances
Published
2025-10-31
DOI
https://doi.org/10.1126/sciadv.adx7431
Citations
1
Primary Topic
Barrier Structure and Function Studies
Type
article
Field-Weighted Citation Impact
0.84
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article

Functional landscape of mechanistic diversity in 27 claudin family members at tight junctions

Hiroshi Suzuki, Tomoki Nishida, Kazuto Tsukita, Gen Shiratsuchi et al.
1 citations
Science Advances
Barrier Structure and Function Studies
0.84
article

Functional landscape of mechanistic diversity in 27 claudin family members at tight junctions

Hiroshi Suzuki, Tomoki Nishida, Kazuto Tsukita, Gen Shiratsuchi, Yoshinori Fujiyoshi, Fabian Eisenstein, Sachiko Tsukita, Koji Aoyama, Mayumi Hamasaki, Manabu Kitamata, Takeshi Yagi, Tatsuya Katsuno, Radostin Danev, Hiroka Kashihara, Shun Nakamura, Atsushi Tamura, Hiroo Tanaka
article en
1 citations

Abstract

The diversity of epithelial paracellular barriers, essential for various biological functions, is primarily determined by the combination of 27 claudins (Cldns) that form tight junctions (TJs). However, the basis of their functional diversity remains largely unexplored. Here, we generated complete <i>Cldn</i>-null mouse epithelial cells to reconstitute the TJ paracellular barrier (TJ barrier) with individual Cldns. Each Cldn establishes its respective TJ barrier, either autonomously or nonautonomously, exhibiting distinct ion conductivity and selectivity. Clustering algorithms revealed a previously unidentified classification of Cldns into four main classes with well-defined subclasses, moving beyond the conventional paracellular barrier-versus-channel-forming dichotomy. Our findings, including the in vivo Cldn dynamics, provide a framework for understanding TJ barrier diversity and plasticity, offering insights into organ-specific homeostasis and guiding therapeutic strategies targeting TJ barriers in health and disease.

Science AdvancesVol. 11(44)
Kyoto University (JP), Textile Research Institute (US), The University of Tokyo (JP), Teikyo University (JP), The University of Osaka (JP)
Openalex Percentile: Top 20%
Barrier Structure and Function Studies
0.84
DOIOpen Access PDFOpenAlex
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