Angiomotins protein stability at the core of YAP/TAZ mechanotransduction

YAP and TAZ are two highly conserved transcriptional regulators that orchestrate cell transcriptional responses to external mechanical perturbations. Mechanical cues are perceived at Focal Adhesions sites and transmitted within the cell cytoplasm through the F-actin cytoskeleton, that gets profoundly re-shaped according to mechanical stretching. Changes in the F-actin spatial organization are eventually conveyed from the cell cytoplasm to the nucleus by YAP/TAZ, which shuttle between the two subcellular compartments according to the mechanical state of the cell. Impairment of the F-actin integrity or contractile ability has been shown to blunt YAP/TAZ transcriptional activity and nuclear localization, highlighting the prominent role of the microfilaments network in dictating YAP/TAZ function. However, the exact mechanism through which the F-actin cytoskeleton impacts on YAP/TAZ activation has for long remained a major “black box” in mechanobiology. In this work, through screening of F-actin interactors, we dissected the molecular players that are at the cornerstone of YAP/TAZ responses to modifications in F-actin organization contractility, eventually providing the missing link between F-actin remodeling upon mechanical stimulation and YAP/TAZ activation.