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 Satoshi Konishi
A1 Tomoki Yano
A1 Hiroo Tanaka
A1 Tomoaki Mizuno
A1 Hatsuho Kanoh
A1 Kazuto Tsukita
A1 Toshinori Namba
A1 Atsushi Tamura
A1 Shigenobu Yonemura
A1 Shimpei Gotoh
A1 Hisako Matsumoto
A1 Toyohiro Hirai
A1 Sachiko Tsukita
YR 2019
UL https://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.