OSCA/TMEM63 are an Evolutionarily Conserved Family of Mechanically Activated Ion Channels

Mechanotransduction, the conversion of mechanical cues into biochemical signals, is crucial for many biological processes in plants and animals ^1,2 . In mammals, some mechanosensory processes such as touch sensation and vascular development are mediated by the PIEZO family of mechanically activated (MA) ion channels ^3-5 . In plants, the impact of gravity or soil properties on root development, wind on stem growth, and turgor pressure on plant-cell size and shape are proposed to involve activation of MA ion channels ^6,7 . Homologues of the bacterial MA channel MscS (MSLs) exist in plants, and MSL8 is shown to be involved in pollen hydration ⁸ ; however, the identity of the MA channels required for most mechanotransduction processes in plants have remained elusive ⁹ . Here, we identify various members of the 15 OSCA proteins from Arabidopsis thaliana (previously reported as hyperosmolarity sensors ^10,11 ) as MA ion channels. Purification and reconstitution of OSCA1.2 in liposomes induced stretch-activated currents, suggesting that OSCAs are inherently mechanosensitive, pore-forming ion channels. This conclusion is confirmed by a high-resolution electron microscopy structure of OSCA1.2 described in a companion paper ¹² . Beyond plants, we present evidence that fruit fly, mouse, and human TMEM63 family of proteins, homologues of OSCAs, induce MA currents when expressed in naïve cells. Our results suggest that OSCA/TMEM63 proteins are the largest family of MA ion channels identified, and are conserved across eukaryotes. We anticipate that further characterization of OSCA isoforms which have diverse biophysical properties, will help gain substantial insight on the molecular mechanism of MA ion channel gating and permeation. OSCA1.1 mutant plants have impaired leaf and root growth under stress, potentially linking this ion channel to a mechanosensory role ¹¹ . We expect future studies to uncover novel roles of OSCA/TMEM63 channels in mechanosensory processes across plants and animals.