Dynamin 2 orchestrates YAP/TAZ mechanotransduction via cortical actin remodeling

Mechanotransduction, the process by which cells sense and respond to mechanical stimuli, relies on cell adhesion, actin cytoskeleton remodeling, and biochemical signal integration. Here, we demonstrate that dynamin 2 (DNM2), clathrin plaques and surrounding branched actin filaments are mechanotransduction platforms that regulate YAP/TAZ signaling. We show that branched actin filaments surrounding clathrin plaques recruit TAZ, whereas contractile stress fibers associated with focal adhesions promote YAP localization. DNM2, the actin capping protein gelsolin, YAP and TAZ organize the cortical actin network around clathrin plaques while actin disorganization due to DNM2 or clathrin depletion delocalize both YAP and TAZ. In centronuclear myopathy models, DNM2 mutations impair actin remodeling, leading to aberrant YAP/TAZ nuclear translocation and altered gene expression of their transcriptional targets. Importantly, allele-specific mutant DNM2 silencing restores YAP/TAZ balance, actin organization and normalizes gene expression. Our findings establish clathrin plaques and DNM2 as central regulators of YAP/TAZ-mediated mechanotransduction.