Joining forces: crosstalk between mechanosensitive PIEZO1 ion channels and integrin-mediated focal adhesions

Both integrin-mediated focal adhesions (FAs) and mechanosensitive ion channels such as PIEZO1 are critical in mechanotransduction processes that influence cell differentiation, development, and cancer. Ample evidence now exists for regulatory crosstalk between FAs and PIEZO1 channels with the molecular mechanisms underlying this process remaining unclear. However, an emerging picture is developing based on spatial crosstalk between FAs and PIEZO1 revealing a synergistic model involving the cytoskeleton, extracellular matrix (ECM) and calcium-dependent signaling. Already cell type, cell contractility, integrin subtypes and ECM composition have been shown to regulate this crosstalk, implying a highly fine-tuned relationship between these two major mechanosensing systems. In this review, we summarize the latest advances in this area, highlight the physiological implications of this crosstalk and identify gaps in our knowledge that will improve our understanding of cellular mechanosensing.