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. 2024 May 6;223(5):e202307104.
doi: 10.1083/jcb.202307104. Epub 2024 Mar 22.

Tight junction membrane proteins regulate the mechanical resistance of the apical junctional complex

Thanh Phuong Nguyen  1   2 , Tetsuhisa Otani  1   2   3 , Motosuke Tsutsumi  4   5 , Noriyuki Kinoshita  6   7 , Sachiko Fujiwara  1   2 , Tomomi Nemoto  2   4   5 , Toshihiko Fujimori  6   7 , Mikio Furuse  1   2   8
Affiliations

Tight junction membrane proteins regulate the mechanical resistance of the apical junctional complex

Thanh Phuong Nguyen et al. J Cell Biol. .

Abstract

Epithelia must be able to resist mechanical force to preserve tissue integrity. While intercellular junctions are known to be important for the mechanical resistance of epithelia, the roles of tight junctions (TJs) remain to be established. We previously demonstrated that epithelial cells devoid of the TJ membrane proteins claudins and JAM-A completely lack TJs and exhibit focal breakages of their apical junctions. Here, we demonstrate that apical junctions fracture when claudin/JAM-A-deficient cells undergo spontaneous cell stretching. The junction fracture was accompanied by actin disorganization, and actin polymerization was required for apical junction integrity in the claudin/JAM-A-deficient cells. Further deletion of CAR resulted in the disruption of ZO-1 molecule ordering at cell junctions, accompanied by severe defects in apical junction integrity. These results demonstrate that TJ membrane proteins regulate the mechanical resistance of the apical junctional complex in epithelial cells.

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Conflict of interest statement

Disclosures: T. Otani reported grants from Inamori Foundation, the Japan Spina Bifida and Hydrocephalus Research Foundation, and Takeda Science Foundation during the conduct of the study and personal fees from Nikon Solutions Co., Ltd. outside the submitted work. M. Furuse reported grants from Kobayashi Pharmaceutical Co., Ltd. outside the submitted work; in addition, M. Furuse had patent 7408134 licensed “National Institutes of Natural Sciences.” No other disclosures were reported.

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