PT  - JOURNAL ARTICLE
AU  - Satoshi Konishi
AU  - Tomoki Yano
AU  - Hiroo Tanaka
AU  - Tomoaki Mizuno
AU  - Hatsuho Kanoh
AU  - Kazuto Tsukita
AU  - Toshinori Namba
AU  - Atsushi Tamura
AU  - Shigenobu Yonemura
AU  - Shimpei Gotoh
AU  - Hisako Matsumoto
AU  - Toyohiro Hirai
AU  - Sachiko Tsukita
TI  - Vinculin is critical for the robustness of the epithelial cell sheet paracellular barrier for ions
AID  - 10.26508/lsa.201900414
DP  - 2019 Aug 01
TA  - Life Science Alliance
PG  - e201900414
VI  - 2
IP  - 4
4099  - https://www.life-science-alliance.org/content/2/4/e201900414.short
4100  - https://www.life-science-alliance.org/content/2/4/e201900414.full
SO  - Life Sci. Alliance2019 Aug 01; 2
AB  - The paracellular barrier function of tight junctions (TJs) in epithelial cell sheets is robustly maintained against mechanical fluctuations, by molecular mechanisms that are poorly understood. Vinculin is an adaptor of a mechanosensory complex at the adherens junction. Here, we generated vinculin KO Eph4 epithelial cells and analyzed their confluent cell-sheet properties. We found that vinculin is dispensable for the basic TJ structural integrity and the paracellular barrier function for larger solutes. However, vinculin is indispensable for the paracellular barrier function for ions. In addition, TJs stochastically showed dynamically distorted patterns in vinculin KO cell sheets. These KO phenotypes were rescued by transfecting full-length vinculin and by relaxing the actomyosin tension with blebbistatin, a myosin II ATPase activity inhibitor. Our findings indicate that vinculin resists mechanical fluctuations to maintain the TJ paracellular barrier function for ions in epithelial cell sheets.