Abstract
Large flat clathrin plaques are stable features of the plasma membrane associated with sites of strong adhesion suggesting that they could also play a role in force transduction. Here, we analyzed how clathrin plaques interact with the cytoskeleton and how they respond to mechanical cues in skeletal muscle myotubes. We show that branched actin networks surrounding clathrin plaques are directly regulated by dynamin 2, anchor intermediate filaments and sequester YAP/TAZ mechanotransducers at the plasma membrane. Dynamin 2, clathrin and desmin intermediate filaments are all required for basal YAP/TAZ nucleo/cytoplasmic distribution and efficient nuclear translocation in response to mechanical stimuli. Dynamin 2 mutations that are responsible for centronuclear myopathy in humans disorganize the desmin network and deregulate YAP/TAZ signaling both in vitro and in vivo. Thus, clathrin plaques and associated dynamin 2 act as sensors conveying mechanical cues and integrate cell signaling with cytoskeletal regulation.