The mechano-sensitive response of β1 integrin promotes SRC-positive late endosome recycling and activation of Yes-associated protein.
Fiche publication
Date publication
juillet 2020
Journal
The Journal of biological chemistry
Auteurs
Membres identifiés du Cancéropôle Est :
Dr RONDE Philippe
Tous les auteurs :
Block MR, Brunner M, Ziegelmeyer T, Lallemand D, Pezet M, Chevalier G, Rondé P, Gauthier-Rouviere C, Wehrle-Haller B, Bouvard D
Lien Pubmed
Résumé
Yes-associated protein (YAP) signaling has emerged as a crucial pathway in several normal and pathological processes. Although the main upstream effectors that regulate its activity have been extensively studied, the role of the endosomal system has been far less characterized. Here, we identified the late endosomal/lysosomal adaptor MAPK and mTOR activator (LAMTOR) complex as an important regulator of YAP signaling in a preosteoblast cell line. We found that p18/LAMTOR1-mediated peripheral positioning of late endosomes allows delivery of SRC proto-oncogene, non-receptor tyrosine kinase (SRC) to the plasma membrane and promotes activation of a SRC-dependent signaling cascade that controls YAP nuclear shuttling. Moreover, β1 integrin engagement and mechano-sensitive cues, such as external stiffness and related cell contractility, controlled LAMTOR targeting to the cell periphery and thereby late endosome recycling, and had a major impact on YAP signaling. Our findings identify the late endosome recycling pathway as a key mechanism that controls YAP activity and explains YAP mechano-sensitivity.
Mots clés
LAMTOR complex, Late endosomes, Src, cell adhesion, cell signaling, extracellular matrix, mechanosensing, vesicular trafficking, yes-associated protein (YAP)
Référence
J. Biol. Chem.. 2020 Jul 19;: