Mechano-adaptive sensory mechanism of ?-catenin under tension.

ABSTRACT: The contractile forces in individual cells drive the tissue processes, such as morphogenesis and wound healing, and maintain tissue integrity. In these processes, ?-catenin molecule acts as a tension sensor at cadherin-based adherens junctions (AJs), accelerating the positive feedback of intercellular tension. Under tension, ?-catenin is activated to recruit vinculin, which recruits actin filaments to AJs. In this study, we revealed how ?-catenin retains its activated state while avoiding unfolding under tension. Using single-molecule force spectroscopy employing atomic force microscopy (AFM), we found that mechanically activated ?-catenin fragment had higher mechanical stability than a non-activated fragment. The results of our experiments using mutated and segmented fragments showed that the key intramolecular interactions acted as a conformational switch. We also found that the conformation of ?-catenin was reinforced by vinculin binding. We demonstrate that ?-catenin adaptively changes its conformation under tension to a stable intermediate state, binds to vinculin, and finally settles into a more stable state reinforced by vinculin binding. Our data suggest that the plastic characteristics of ?-catenin, revealed in response to both mechanical and biochemical cues, enable the functional-structural dynamics at the cellular and tissue levels.

SUBMITTER: Maki K 

PROVIDER: S-EPMC4843013 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature