Browsing by Author "Alegría Fuentes, Juan José"

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    Alternative molecular mechanisms for force transmission at adherens junctions via β-catenin-vinculin interaction
    (2024) Morales-Camilo, Nicole; Liu, Jingzhun; Ramírez Contador, Manuel José; Canales Salgado, Patricio Andrés; Alegría Fuentes, Juan José; Liu, Xuyao; Ong, Ting Ong; Barrera Rojas, Nelson Patricio; Fierro Huerta, Angélica María; Toyama, Yusuke; Goult, Benjamin; Wang, Yilin; Meng, Yue; Nishimura, Ryosuke; Fong-Ngern, Kedsarin; Low, Christine Siok Lan; Kanchanawong, Pakorn; Yan, Jie; Ravasio, Andrea; Bertocchi, Cristina
    Force transmission through adherens junctions (AJs) is crucial for multicellular organization, wound healing and tissue regeneration. Recent studies shed light on the molecular mechanisms of mechanotransduction at the AJs. However, the canonical model fails to explain force transmission when essential proteins of the mechanotransduction module are mutated or missing. Here, we demonstrate that, in absence of α-catenin, β-catenin can directly and functionally interact with vinculin in its open conformation, bearing physiological forces. Furthermore, we found that β-catenin can prevent vinculin autoinhibition in the presence of α-catenin by occupying vinculin´s head-tail interaction site, thus preserving force transmission capability. Taken together, our findings suggest a multi-step force transmission process at AJs, where α-catenin and β-catenin can alternatively and cooperatively interact with vinculin. This can explain the graded responses needed to maintain tissue mechanical homeostasis and, importantly, unveils a force-bearing mechanism involving β-catenin and extended vinculin that can potentially explain the underlying process enabling collective invasion of metastatic cells lacking α-catenin.