ArticleThe Journal of cell biology2023
EpCAM proteolysis and release of complexed claudin-7 repair and maintain the tight junction barrier.
Article in The Journal of cell biology, 2023. 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, 33 citations in OpenAlex.
- Article
- Tight junction structure, assembly and (dys)function.Nature reviews. Molecular cell biology · 2026Review
- Matriptase proteolysis selectively drives disassembly and internalization of the claudin-7 complex while preserving E-cadherin.Human cell · 2026Article
- PAK4 promotes vertex remodeling to maintain epithelial integrity and barrier function.bioRxiv : the preprint server for biology · 2025Article
- Article
- Molecular determinants of neuroprotection in blood-brain interfaces of the cynomolgus monkey.Frontiers in pharmacology · 2025Article
- Molecular basis of proteolytic cleavage regulation by the extracellular matrix receptor dystroglycan.Structure (London, England : 1993) · 2024Article
- Loss of intermicrovillar adhesion factor CDHR2 impairs basolateral junctional complexes in transporting epithelia.Molecular biology of the cell · 2024Article
- Regulation of the Function and Expression of EpCAM.Biomedicines · 2024Review
- Tight junction membrane proteins regulate the mechanical resistance of the apical junctional complex.The Journal of cell biology · 2024Article
- Tmprss2 maintains epithelial barrier integrity and transepithelial sodium transport.Life science alliance · 2024Article
- Article
- Matrix metalloproteinase-7 and claudin-7 as novel identified therapeutic targets for restoration of intestinal epithelial barrier in inflammatory bowel diseases.Tissue barriers · 2024Article
- Article
- Early-onset tufting enteropathy in HAI-2-deficient mice is independent of matriptase-mediated cleavage of EpCAM.Development (Cambridge, England) · 2023Article
- ZnUMBA - a live imaging method to detect local barrier breaches.Journal of cell science · 2023Article
- Claudin Barriers on the Brink: How Conflicting Tissue and Cellular Priorities Drive IBD Pathogenesis.International journal of molecular sciences · 2023Review
- Breaking the Gingival Barrier in Periodontitis.International journal of molecular sciences · 2023Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TJs maintain the epithelial barrier by regulating paracellular permeability. Since TJs are under dynamically fluctuating intercellular tension, cells must continuously survey and repair any damage. However, the underlying mechanisms allowing cells to sense TJ damage and repair the barrier are not yet fully understood. Here, we showed that proteinases play an important role in the maintenance of the epithelial barrier. At TJ break sites, EpCAM-claudin-7 complexes on the basolateral membrane become accessible to apical membrane-anchored serine proteinases (MASPs) and the MASPs cleave EpCAM. Biochemical data and imaging analysis suggest that claudin-7 released from EpCAM contributes to the rapid repair of damaged TJs. Knockout (KO) of MASPs drastically reduced barrier function and live-imaging of TJ permeability showed that MASPs-KO cells exhibited increased size, duration, and frequency of leaks. Together, our results reveal a novel mechanism of TJ maintenance through the localized proteolysis of EpCAM at TJ leaks, and provide a better understanding of the dynamic regulation of epithelial permeability.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.