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Title: Mechano-adaptive sensory mechanism of α-catenin under tension
Authors: Maki, Koichiro  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-7607-2903 (unconfirmed)
Han, Sung-Woong
Hirano, Yoshinori
Yonemura, Shigenobu
Hakoshima, Toshio
Adachi, Taiji  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0001-5280-4156 (unconfirmed)
Author's alias: 牧, 功一郎
安達, 泰治
Keywords: Biological physics
Molecular conformation
Single-molecule biophysics
Issue Date: 25-Apr-2016
Publisher: Springer Nature
Journal title: Scientific Reports
Volume: 6
Thesis number: 24878
Abstract: The contractile forces in individual cells drive the tissue processes, such as morphogenesis and wound healing, and maintain tissue integrity. In these processes, α-catenin molecule acts as a tension sensor at cadherin-based adherens junctions (AJs), accelerating the positive feedback of intercellular tension. Under tension, α-catenin is activated to recruit vinculin, which recruits actin filaments to AJs. In this study, we revealed how α-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 α-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 α-catenin was reinforced by vinculin binding. We demonstrate that α-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 α-catenin, revealed in response to both mechanical and biochemical cues, enable the functional-structural dynamics at the cellular and tissue levels.
Rights: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
URI: http://hdl.handle.net/2433/226847
DOI(Published Version): 10.1038/srep24878
PubMed ID: 27109499
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