Piezo - the mechanosensor
Piezo proteins (piezo1 and piezo2) are evolutionarily conserved transmembrane proteins (24-40 domains) which are involved in mechanotransduction in mammalian cells and function as mechanosensor. Piezo proteins are 2500-2800 amino acids long and are identified as mechanically activated ion channels(MA) / mechanosensitive channels that are encoded by FAM 38 genes. Piezo proteins mediate mechanosensory transduction i.e. conversion of mechanical forces into biological signals which is a very important physiologic process for all types of mammalian cells. This mechanotransduction regulates vital processes in mammals including embryonic development, blood pressure regulation, various sensations such as touch, hearing, pain, proprioception, urine flow regulation, cell migration, proliferation and elongation, bladder distension, vascular tone regulation, sensation of shear stress etc. All organisms have mechanosensitive channels which are directly gated by forces to convert mechanical stimuli into electrical signals in mechanosensory transduction. The 3 important mechanical sensory modalities are touch, hearing and proprioception that are mediated by mechanosensory channels. These channels open very rapidly with short latency (<5 milliseconds) and directly gated by forces [1].
Piezo1 is expressed with high levels in erythrocytes, endothelial cells and periodontal ligament cells in skin, lung, bladder, and kidney. Piezo2 is mostly expressed in sensory trigeminal ganglia (TG) and dorsal root ganglia (DRG), Merkel cells (epidermal mechanoreceptor involved in touch), lung and bladder. Piezo 1 acts as an endothelial sensor of blood flow, promotes endothelial cell organization, regulates erythrocyte volume, maintains structural integrity of red cells, detects urothelial extension during bladder distension, regulates stretch activated calcium pathway and also acts as an osmoreceptor in erythrocytes [2]. Piezo2 is involved in mechanosensation (such as light, touch and noxious stimuli) and somatosensation through cutaneous mechanoreceptor.
Mutation in human piezo protein results in various disorders including hereditary xerocytosis (a dominant disorder of erythrocyte dehydration results from missense mutation in piezo1) and different types of neuromuscular disorders such as distal arthrogryposis type 5 (another dominant disorder characterized by skeletal muscle contractures and restrictive lung disease), Gordon syndrome (piezo 2 mutation) etc. A new study from Scripps research institute suggests that Piezo1 could help to design better pain medication and future therapies for blood disorders and hypertension because piezo proteins can control the sensation of touch / sense force by detecting tension in the cell membrane [3].
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