Piezo1, the new actor in cell volume regulation

All animal cells control their volume through a complex set of mechanisms, both to counteract osmotic perturbations of the environment and to enable numerous vital biological processes, such as proliferation, apoptosis, and migration. The ability of cells to adjust their volume depends on the activity of ion channels and transporters which, by moving K⁺, Na⁺, and Cl^- ions across the plasma membrane, generate the osmotic gradient that drives water in and out of the cell. In 2010, Patapoutian's group identified a small family of evolutionarily conserved, Ca²⁺-permeable mechanosensitive channels, Piezo1 and Piezo2, as essential components of the mechanically activated current that mediates mechanotransduction in vertebrates. Piezo1 is expressed in several tissues and its opening is promoted by a wide range of mechanical stimuli, including membrane stretch/deformation and osmotic stress. Piezo1-mediated Ca²⁺ influx is used by the cell to convert mechanical forces into cytosolic Ca²⁺ signals that control diverse cellular functions such as migration and cell death, both dependent on changes in cell volume and shape. The crucial role of Piezo1 in the regulation of cell volume was first demonstrated in erythrocytes, which need to reduce their volume to pass through narrow capillaries. In HEK293 cells, increased expression of Piezo1 was found to enhance the regulatory volume decrease (RVD), the process whereby the cell re-establishes its original volume after osmotic shock-induced swelling, and it does so through Ca²⁺-dependent modulation of the volume-regulated anion channels. More recently we reported that Piezo1 controls the RVD in glioblastoma cells via the modulation of Ca²⁺-activated K⁺ channels. To date, however, the mechanisms through which this mechanosensitive channel controls cell volume and maintains its homeostasis have been poorly investigated and are still far from being understood. The present review aims to provide a broad overview of the literature discussing the recent advances on this topic.