Mechano-adaptive sensory mechanism of α-catenin under tension.
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.
Department of Biomechanics, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo, Kyoto 606-8507, Japan.|Department of Micro Engineering, Graduate School of Engineering, Kyoto University, Yoshida Honmachi, Sakyo, Kyoto 606-8501, Japan.
Koichiro
K
Maki
National Institute for Nanomaterials Technology, Pohang University of Science and Technology, 77 Cheongam-ro, Nam-Gu, Pohang, Gyeongbuk 790-784, Korea.
Sung-Woong
SW
Han
Structural Biology Laboratory, Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
Yoshinori
Y
Hirano
Ultrastructural Research Team, RIKEN Center for Life Science Technologies, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
Shigenobu
S
Yonemura
Structural Biology Laboratory, Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0192, Japan.
Toshio
T
Hakoshima
Department of Biomechanics, Institute for Frontier Medical Sciences, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo, Kyoto 606-8507, Japan.|Department of Micro Engineering, Graduate School of Engineering, Kyoto University, Yoshida Honmachi, Sakyo, Kyoto 606-8501, Japan.
Taiji
T
Adachi
D022005:Adherens Junctions / Q000378:metabolism; D000818:Animals; D055595:Mechanical Phenomena; D040542:Mechanotransduction, Cellular; D051379:Mice; D018625:Microscopy, Atomic Force; D011487:Protein Conformation; D017510:Protein Folding; D000072760:Single Molecule Imaging; D051178:alpha Catenin / Q000378:metabolism*
D051178:alpha Catenin