Structural Designs and Mechanogating Mechanisms of the Mechanosensitive Piezo Channels

Mechanotransduction by ion channels converts mechanical forces into biological signals. Piezo1 is a versatile mechanotransduction channel for initiating Ca2+ signaling in various non-excitable cell types, and Piezo2 mainly functions in sensory neurons and specialized cell types such as Merkel cells for sensing touch, tactile pain, balance, breath, blood pressure, and bladder fullness. Piezo1/2 form a three-bladed, propeller-like homotrimeric structure with the signature nano-bowl configuration of the highly curved TM region consisting of a total of 114 TM helices. Recent studies show that Piezo channels might utilize a dual-gating mechanism, in which the TM gate might be regulated by the top cap, while the lateral plug gates are controlled by the blade beam via an elegant plug-and-latch mechanism. Emerging models, including force-from-lipids and force-from-filament models, show how Piezo channels may respond to local changes of membrane curvature and tension and long-range mechanical perturbation across a cell. The evolutionarily conserved Piezo channel family, including Piezo1 and Piezo2 in mammals, serves as versatile mechanotransducers in various cell types and consequently governs fundamental pathophysiological processes ranging from vascular development to the sense of gentle touch and tactile pain. Piezo1/2 possess a unique 38-transmembrane (TM) helix topology and form a homotrimeric propeller-shaped structure comprising a central ion-conducting pore and three peripheral mechanosensing blades. The unusually curved TM region of the three blades shapes a signature nano-bowl configuration with potential to generate large in-plane membrane area expansion, which might confer exquisite mechanosensitivity to Piezo channels. Here, we review the current understanding of Piezo channels with a particular focus on their unique structural designs and elegant mechanogating mechanisms. The evolutionarily conserved Piezo channel family, including Piezo1 and Piezo2 in mammals, serves as versatile mechanotransducers in various cell types and consequently governs fundamental pathophysiological processes ranging from vascular development to the sense of gentle touch and tactile pain. Piezo1/2 possess a unique 38-transmembrane (TM) helix topology and form a homotrimeric propeller-shaped structure comprising a central ion-conducting pore and three peripheral mechanosensing blades. The unusually curved TM region of the three blades shapes a signature nano-bowl configuration with potential to generate large in-plane membrane area expansion, which might confer exquisite mechanosensitivity to Piezo channels. Here, we review the current understanding of Piezo channels with a particular focus on their unique structural designs and elegant mechanogating mechanisms. also known as hereditary xerocytosis; a hemolytic anemia characterized by primary erythrocyte dehydration, resulting in increased fragility of red blood cells. an inherited skeletal muscle disorder with congenital joint contracture in two or more areas of the body, particularly in distal extremities, including hands and feet. also referred to as tether model which proposes that the channel is physically tethered to extracellular matrix or intracellular accessory structures such as cytoskeleton for mechanogating. this model proposes that mechanical stimuli can be transmitted directly to the channel via lipid bilayer deformation; in other words, channel directly responds to changes in membrane tension. mutations that confer enhanced or new activity on a protein. also designated as distal arthrogryposis type 3; a rare genetic disorder characterized by cleft palate and congenital contractures of the hands and feet. here, it defines that the TM region resides in a flat planar bilayer membrane. mutations that result in abolished or reduced protein function. a congenital maldevelopment of the lymphatic system, resulting in an effusion of chyle or lymph into the limbs and pleural or peritoneal cavity. a genetic connective tissue disorder. Patients with this disorder typically have a distinct facial expression, a cleft or high-arched palate, small or receding jaw, bone joints in a fixed position, growth delay, and limited control of muscle movement. a painful sensation caused by innocuous stimuli like light touch. the plane across the middle of the bilayer membrane. the pressure required for half maximal activation. also known as kinesthesia; the sense of self-movement and body position. It is the reason we are able to move freely without consciously thinking about the environment. a medical condition in which a person’s spine has a sideways curve. the tension required for half maximal activation. also termed single-channel conductance; a natural measure of the ability of a single opened channel to allow ions to move through.