α-catenin switches between a slip and an asymmetric catch bond with F-actin to cooperatively regulate cell junction fluidity
Year: 2022
Authors: Arbore C., Sergides M., Gardini L., Bianchi G., Kashchuk AV., Pertici I., Bianco P., Pavone FS., Capitanio M.
Autors Affiliation: Univ Florence, LENS European Lab Nonlinear Spect, Via Nello Carrara 1, I-50019 Sesto Fiorentino, Italy; Univ Florence, Dept Phys & Astron, Via Sansone 1, I-50019 Sesto Fiorentino, Italy; Univ Cyprus, Dept Phys, POB 20537, CY-1678 Nicosia, Cyprus; CNR, Natl Inst Opt, Largo Fermi 6, I-50125 Florence, Italy; Univ Florence, Dept Biol, Via Madonna Piano 6, I-50019 Sesto Fiorentino, Italy.
Abstract: By using laser tweezers, the authors show that a single alpha-catenin molecule does not resist force on F-actin. However, clustering of multiple molecules and force applied toward F-actin pointed end engage a molecular switch in alpha-catenin, which unfolds and strongly binds F-actin. alpha-catenin is a crucial protein at cell junctions that provides connection between the actin cytoskeleton and the cell membrane. At adherens junctions (AJs), alpha-catenin forms heterodimers with beta-catenin that are believed to resist force on F-actin. Outside AJs, alpha-catenin forms homodimers that regulates F-actin organization and directly connect the cell membrane to the actin cytoskeleton, but their mechanosensitive properties are inherently unknown. By using ultra-fast laser tweezers we found that a single alpha-beta-catenin heterodimer does not resist force but instead slips along F-actin in the direction of force. Conversely, the action of 5 to 10 alpha-beta-catenin heterodimers together with force applied toward F-actin pointed end engaged a molecular switch in alpha-catenin, which unfolded and strongly bound F-actin as a cooperative catch bond. Similarly, an alpha-catenin homodimer formed an asymmetric catch bond with F-actin triggered by protein unfolding under force. Our data suggest that alpha-catenin clustering together with intracellular tension engage a fluid-to-solid phase transition at the membrane-cytoskeleton interface.
Journal/Review: NATURE COMMUNICATIONS
Volume: 13 (1) Pages from: 1146-1 to: 1146-11
More Information: We thank Dr. Noboru Ishiyama for the pET28a vector containing mouse alpha E-catenin. This work was supported by the European Union’s Horizon 2020 research and innovation program under grant agreement no 871124 Laserlab-Europe, by the Italian Ministry of University and Research (FIRB Futuro in Ri cerca 2013 grant n. RBFR13V4M2), the University of Florence grant MURPASS, and by Ente Cassa di Risparmio di Firenze. A.V. Kashchuk was supported by the Human Frontier Science Program Cross-Disciplinary Fellowship LT008/2020-C.KeyWords: Binding; Filament; Protein; MyosinDOI: 10.1038/s41467-022-28779-7ImpactFactor: 16.600Citations: 20data from “WEB OF SCIENCE” (of Thomson Reuters) are update at: 2024-09-15References taken from IsiWeb of Knowledge: (subscribers only)
