RT Journal Article SR Electronic T1 Vinculin is critical for the robustness of the epithelial cell sheet paracellular barrier for ions JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e201900414 DO 10.26508/lsa.201900414 VO 2 IS 4 A1 Konishi, Satoshi A1 Yano, Tomoki A1 Tanaka, Hiroo A1 Mizuno, Tomoaki A1 Kanoh, Hatsuho A1 Tsukita, Kazuto A1 Namba, Toshinori A1 Tamura, Atsushi A1 Yonemura, Shigenobu A1 Gotoh, Shimpei A1 Matsumoto, Hisako A1 Hirai, Toyohiro A1 Tsukita, Sachiko YR 2019 UL http://www.life-science-alliance.org/content/2/4/e201900414.abstract 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.