Inside-out regulation of E-cadherin conformation and adhesion

• DOI: 10.1073/pnas.2104090118
• Publication Date: 2021-07-22T19:50:32Z
• Authors: Ramesh Koirala; Andrew Vae Priest; Chi-Fu Yen; Joleen S. Cheah; Willem-Jan Pannekoek; Martijn Gloerich; Soichiro Yamada; Sanjeevi Sivasankar
• Keywords: conformation; 0301 basic medicine; 570; inside-out regulation; 1.1 Normal biological development and functioning; Madin Darby Canine Kidney Cells; 03 medical and health sciences; Dogs; Research Support, N.I.H., Extramural; Journal Article; Cell Adhesion; Animals; ectodomain; Cytoskeleton; Myosin Type II; vinculin; Research Support, Non-U.S. Gov't; E-cadherin; Biological Sciences; Cadherins; Actins; Vinculin; 3. Good health; Myosin Type II/metabolism; Actins/metabolism; Cadherins/chemistry; Biochemistry and Cell Biology; Generic health relevance; Research Support, U.S. Gov't, Non-P.H.S.; Vinculin/metabolism; Protein Binding

Significance Cadherin cell–cell adhesion proteins play key roles in the formation and maintenance of tissues. Their adhesion is carefully regulated to orchestrate complex movement of cells. While cadherin ectodomains bind in two conformations with different adhesive properties, the mechanisms by which cells regulate the conformation (and consequently adhesion) of individual cadherins are unknown. Here, we demonstrate that the association of intracellular vinculin with the cadherin cytoplasmic region regulates cadherin adhesion by switching ectodomains from a weak binding to the strongly adhesive conformation. In contrast to the prevailing view which suggests that vinculin regulates adhesion solely by remodeling the cytoskeleton, we show that vinculin can directly modulate single cadherin ectodomain conformation and this process is mediated by changes in cytoskeletal tension.