Piezo2 is a protein that plays a role in how our bodies interact with and perceive both the external world and internal sensations. It functions as a specialized sensor, detecting physical forces and converting them into signals our nervous system can interpret. This ability to transform mechanical stimuli into electrical messages is crucial for processes from the lightest touch on our skin to the subtle movements that maintain our balance.
The Body’s Mechanical Sensors
Piezo2 is a mechanosensitive ion channel, a protein embedded in cell membranes that responds to mechanical force. When mechanical force deforms the cell membrane, Piezo2 undergoes a conformational change, opening a pore. This opening allows positively charged ions, such as calcium, to flow into the cell. The influx of these ions creates an electrical signal, a process known as mechanotransduction.
The mechanism was elucidated through the work of Ardem Patapoutian’s laboratory at Scripps Research. In 2010, his team identified Piezo1 and Piezo2, advancing the understanding of how mechanical stimuli are detected. Their discovery, which earned Patapoutian a share of the 2021 Nobel Prize, revealed Piezo channels belong to a new family of proteins. Piezo2 is abundant in sensory neurons in the dorsal root ganglia, which are nerve clusters near the spinal cord, and in Merkel cells within the skin.
Piezo2 and Our Sense of Touch
Piezo2 is an important component of our sense of touch and proprioception, which is the body’s ability to sense its position and movement in space. It is found in specialized nerve endings in the skin that detect light touch, gentle pressure, and vibration. For example, Piezo2 allows us to feel the subtle brush of a feather, the texture of fabric, or gentle vibrations from a phone. Mice lacking Piezo2 in their sensory neurons exhibit significant deficits in responding to gentle brush and vibration, while their sensitivity to high-intensity mechanical stimuli remains intact.
Beyond external touch, Piezo2 is also the primary mechanotransducer for proprioception. This involves sensing the stretch and tension in muscles, tendons, skin, and joints. Without functional Piezo2, the ability to perceive the position of limbs and body parts without visual input is severely impaired, leading to uncoordinated movements and abnormal limb positioning. This highlights Piezo2’s role in maintaining balance and enabling coordinated actions in daily life.
Beyond Touch: Internal Sensing
The functions of Piezo2 extend beyond external touch and proprioception to include internal bodily processes. This protein helps the body maintain homeostasis, which is the stable internal environment necessary for survival. Piezo2 plays a role in sensing the stretch of internal organs.
Piezo2 is involved in the sensation of bladder fullness, helping to regulate urination. It also senses airway stretch, which is important for regulating breathing. Individuals with certain Piezo2 mutations can exhibit shallow breathing during infancy, underscoring its role in lung inflation sensing. Piezo1 and Piezo2 together are involved in sensing blood pressure through baroreceptors, which are stretch-sensitive neurons in the walls of arteries. These mechanosensors contribute to the baroreflex, a mechanism that helps regulate heart rate and blood pressure to ensure consistent blood flow throughout the body.
Implications of Piezo2 Dysfunction
When Piezo2 does not function correctly due to genetic mutations, it can lead to neurological and physical disorders. Mutations in the PIEZO2 gene can cause various forms of distal arthrogryposis, a condition characterized by congenital contractures, particularly affecting the hands and feet. These mutations can be either “loss-of-function,” where the protein’s activity is reduced or absent, or “gain-of-function,” where the protein’s activity is altered or increased.
Loss-of-function mutations in Piezo2 are associated with impaired proprioception and tactile sense, leading to symptoms such as hypotonia (low muscle tone), delayed motor milestones, and progressive scoliosis. Individuals with such mutations may also experience perinatal respiratory distress and muscle weakness. Conversely, gain-of-function mutations in Piezo2 are linked to specific types of distal arthrogryposis, such as Gordon syndrome (distal arthrogryposis type 3) and Marden-Walker syndrome, which include contractures of the hands and feet, scoliosis, and sometimes ophthalmoplegia. These conditions demonstrate the impact of Piezo2 on sensory perception, motor control, and physical development.