Oral Presentation 2014 International Biophysics Congress

Active junctions: Reconciling contractility and actin homeostasis (#119)

Alpha Yap 1
  1. Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia

Cadherin-based cell-cell interactions are important determinants of tissue organization, both in health and disease. We have long thought of cell-cell adhesion as providing passive resistance to the detachment forces that act upon tissues, most evidently in epithelia. Recently, we have instead come to realize that many of the forces that cadherin junctions experience are generated by the neighbouring cells themselves. Adhesion effectively couples the contractile cytoskeletons of epithelial cells together. Further, cadherin adhesion is not a passive player in this mechanical event. Cadherins serve as potentially instructive platforms (“active agents”) that control many aspects of actin filament homeostasis and myosin regulation that are found at cell-cell junctions. However, generating the actomyosin cytoskeleton at cadherin junctions also carries potential design contradictions: notably, the capacity for contractility to induce actin filament turnover, which we have found to limit contractile stress generation at junctions. Despite this, epithelial cells can overcome stress-induced filament turnover to generate contractile tension at the apical zonulae adherente. We now report a tension-sensitive actin assembly apparatus, comprising the actin-regulatory proteins vinculin and Mena/VASP, which maintains junctional F-actin levels to sustain effective contractility.