ZO-1 Guides Tight Junction Assembly and Epithelial Morphogenesis via Cytoskeletal Tension-Dependent and -Independent Functions

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung

Beitragende

  • Alexis J. Haas - , University College London (Autor:in)
  • Ceniz Zihni - , University College London (Autor:in)
  • Susanne M. Krug - , Charité – Universitätsmedizin Berlin (Autor:in)
  • Riccardo Maraspini - , Max Planck Institute of Molecular Cell Biology and Genetics (Autor:in)
  • Tetsuhisa Otani - , National Institutes of Natural Sciences - National Institute for Physiological Sciences (Autor:in)
  • Mikio Furuse - , National Institutes of Natural Sciences - National Institute for Physiological Sciences (Autor:in)
  • Alf Honigmann - , Max Planck Institute of Molecular Cell Biology and Genetics, Technische Universität Dresden (Autor:in)
  • Maria S. Balda - , University College London (Autor:in)
  • Karl Matter - , University College London (Autor:in)

Abstract

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 disrupted junction assembly and morphogenesis in an ECM stiffness-dependent manner and led to a stiffness-dependant reorganisation of active myosin. Both junction formation and morphogenesis were rescued by inhibition of actomyosin contractility. ZO-1 depletion also impacted mechanical tension at cell-matrix and E-cadherin-based cell–cell adhesions. The effect on E-cadherin also depended on ECM stiffness and correlated with effects of ECM stiffness on actin cytoskeleton organisation. However, ZO-1 knockout also revealed tension-independent functions of ZO-1. ZO-1-deficient cells could assemble functional barriers at low tension, but 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, in a second, tension-independent step, ZO-1 is required to assemble morphologically and structurally fully assembled and functionally normal tight junctions.

Details

OriginalspracheEnglisch
Aufsatznummer3775
FachzeitschriftCells
Jahrgang11
Ausgabenummer23
PublikationsstatusVeröffentlicht - Dez. 2022
Peer-Review-StatusJa
Extern publiziertJa

Externe IDs

PubMed 36497035

Schlagworte

Schlagwörter

  • claudin, ECM, F-actin, freeze fracture, myosin, occludin, stiffness, tension, tight junction, transepithelial electrical resistance