RT Journal Article
SR Electronic
T1 Reciprocal regulation between cell mechanics and ZO-1 guides tight junction assembly and epithelial morphogenesis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.07.17.500023
DO 10.1101/2022.07.17.500023
A1 Alexis J. Haas
A1 Ceniz Zihni
A1 Susanne M. Krug
A1 Riccardo Maraspini
A1 Tetsuhisa Otani
A1 Mikio Furuse
A1 Alf Honigmann
A1 Maria Balda
A1 Karl Matter
YR 2022
UL http://biorxiv.org/content/early/2022/07/18/2022.07.17.500023.abstract
AB Formation and maintenance of tissue barriers require the coordination of cell mechanics and cell-cell junction assembly. Here, we combined methods to modulate ECM stiffness and to measure mechanical forces on adhesion complexes to investigate how tight junctions regulate cell mechanics and epithelial morphogenesis. We found that depletion of the tight junction adaptor ZO-1 regulates cytoskeletal tension at cell-matrix and cell-cell interfaces in an ECM stiffness-regulated manner, possibly via differential organisation of the actin cytoskeleton. ZO-1 depletion inhibited junction assembly and disrupted morphogenesis in an ECM stiffness-dependent manner. Both processes were rescued by inhibition of cell contractility. Although ZO-1-deficient cells could assemble functional barriers at low tension, their tight junctions remained corrupted with strongly reduced and discontinuous recruitment of junctional components. Our results thus reveal that reciprocal regulation between ZO-1 and cell mechanics controls tight junction assembly and epithelial morphogenesis, and that tension-independent roles of ZO-1 control proper junction organisation.Competing Interest StatementThe authors have declared no competing interest.