Exploring the interplay between Piezo1 and YAP/TAZ in mechanotransduction

Mechanical signals are essential factors for cells profoundly impacting their phenotype. Mechanotransduction is the ability of cells to perceive physical and mechanical stimuli from the environment and transduce them into a biological response. Two important families of mechanotransducers are YAP/TAZ transcriptional co-factors and Piezo1-2 mechanosensitive cation channels. Although these proteins have been reported to act in similar biological processes, they are filling different functions in mechanobiology and their relationship is still poorly understood. Thus, here we aim to explore the putative interplay between Piezo1 and YAP/TAZ in the mechanotransduction cascade. Using siRNA against Piezo1, we found that YAP/TAZ activation by classical mechanical signals (i.e. stiff vs soft and sparse vs dense culture conditions) is Piezo1 independent in different cell types (epithelial cells and fibroblast). However, specific Piezo1 gating triggered by treatment with agonist Yoda1 in low mechanical settings (soft or dense) is sufficient to induce a strong transient YAP/TAZ transcriptional activation, suggesting that different mechanical inputs might require Piezo1 to activate YAP/TAZ. Moreover, a positive feedback loop might exist since we found that YAP/TAZ transcriptionally control Piezo1 expression. This work is representing a first step for understanding the connection between mechanosensitive channels and mechanosensitive transcription factors.