掲載種別：研究論文（学術雑誌）   出版者・発行元：Rockefeller University Press  

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.

DOI： 10.1083/jcb.202204079

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Wiley  

Abstract

Occludin, tricellulin, and marvelD3 belong to the tight junction (TJ)‐associated MARVEL protein family. Occludin and tricellulin jointly contribute to TJ strand branching point formation and epithelial barrier maintenance. However, whether marvelD3 has the same function remains unclear. Furthermore, the roles of the carboxy‐terminal cytoplasmic tail, which is conserved in occludin and tricellulin, on the regulation of TJ strand morphology have not yet been explored in epithelial cells. We established tricellulin/occludin/marveld3 triple‐gene knockout (tKO) MDCK II cells and evaluated the roles of marvelD3 in the TJ strand structure and barrier function using MDCK II cells and a mathematical model. The complexity of TJ strand networks and paracellular barrier did not change in tKO cells compared to that in tricellulin/occludin double‐gene knockout (dKO) cells. Exogenous marvelD3 expression in dKO cells did not increase the complexity of TJ strand networks and epithelial barrier tightness. The expression of the carboxy‐terminal truncation mutant of tricellulin restored the barrier function in the dKO cells, whereas occludin lacking the carboxy‐terminal cytoplasmic tail was not expressed on the plasma membrane. These data suggest that marvelD3 does not affect the morphology of TJ strands and barrier function in MDCK II cells and that the carboxy‐terminal cytoplasmic tail of tricellulin is dispensable for barrier improvement.

その他リンク： https://onlinelibrary.wiley.com/doi/full-xml/10.1111/nyas.14889

DOI： 10.1111/nyas.14889

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掲載種別：研究論文（学術雑誌）   出版者・発行元：American Society for Cell Biology (ASCB)  

Tight junctions (TJs) are composed of claudin-based TJ strands. The complexity of TJ strands regulates paracellular permeability of epithelial cells. Occludin and tricellulin contribute to the formation of the complex TJ-strand network possibly by connecting TJ strands and establishment of a tight barrier.

DOI： 10.1091/mbc.e20-07-0464

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Impact Journals, LLC  

DOI： 10.18632/oncotarget.24742

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Japan Society of Mechanical Engineers  

DOI： 10.1299/jbse.16-00670

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Public Library of Science (PLoS)  

DOI： 10.1371/journal.pone.0106853

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier BV  

DOI： 10.1016/j.yexcr.2014.05.002

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

その他リンク： http://link.springer.com/article/10.1007/s10529-013-1391-3/fulltext.html

DOI： 10.1007/s10529-013-1391-3

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掲載種別：研究論文（学術雑誌）   出版者・発行元：Springer Science and Business Media LLC  

その他リンク： http://link.springer.com/article/10.1007/s10529-013-1368-2/fulltext.html

DOI： 10.1007/s10529-013-1368-2

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