Vinculin is critical for the robustness of the epithelial cell sheet paracellular barrier for ions
| Autor: | Tomoaki Mizuno, Shimpei Gotoh, Atsushi Tamura, Toyohiro Hirai, Toshinori Namba, Tomoki Yano, Shigenobu Yonemura, Sachiko Tsukita, Kazuto Tsukita, Satoshi Konishi, Hisako Matsumoto, Hatsuho Kanoh, Hiroo Tanaka |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
animal structures
Health Toxicology and Mutagenesis Plant Science macromolecular substances Biochemistry Genetics and Molecular Biology (miscellaneous) Heterocyclic Compounds 4 or More Rings Cell Line Tight Junctions Adherens junction 03 medical and health sciences Gene Knockout Techniques 0302 clinical medicine Myosin medicine Humans Barrier function Research Articles 030304 developmental biology Ions 0303 health sciences Stochastic Processes Ecology biology Tight junction Chemistry urogenital system HEK 293 cells digestive oral and skin physiology Epithelial Cells Actomyosin Vinculin musculoskeletal system Epithelium medicine.anatomical_structure HEK293 Cells Paracellular transport biology.protein Biophysics 030217 neurology & neurosurgery Research Article |
| Zdroj: | Life Science Alliance |
| ISSN: | 2575-1077 |
| Popis: | Vinculin in the apical junctional complex maintains the paracellular barrier function specifically for ions, but not for large solutes, by buffering mechanical fluctuations. 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. |
| Databáze: | OpenAIRE |
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