PIEZO1-gene

The PIEZO1 gene (PIEZO1 stands for: Piezo-type mechanosensitive ion channel component 1) is a protein-coding gene located on chromosome 16q24.3. The signaling pathways associated with this gene include monoatomic cation channel activity and mechanosensitive monoatomic ion channel activity. This is associated with endothelial cell responses to shear stress and cellular responses to stimuli. An important paralog of this gene is PIEZO2.

The protein encoded by this gene is a mechanically activated ion channel that combines mechanical forces with biological signals. The encoded protein contains 36 transmembrane domains and functions as a homotetramer (Andolfo I et al. 2013). The conductivity for monovalent alkali metal ions is highest for K(+), intermediate for Na(+) and lowest for Li(+). Divalent ions, with the exception of Mn(2+), pass through the channel, but more slowly than monovalent ions, and they also reduce K(+) currents (Gnanasambandam R et al. 2015). Generates currents characterized by a linear current-voltage relationship and sensitive to ruthenium red and gadolinium.

The ion channel plays a key role in epithelial cell adhesion by maintaining integrin activation through R-Ras recruitment to the ER, most likely in its activated state, and subsequent stimulation of calpain signaling (McHugh BJ et al. 2010).

Piezo-channels are homotrimeric, three-bladed, propeller-shaped structures that utilize a cap movement and plug-and-lock mechanism to control their ion-conducting pathways. In the hair cells of the inner ear, the PIEZO1/2 subunits may be part of the mechanotransducing (MET) non-selective cation channel complex, where they may function as a pore-forming ion-conducting component of the complex.

In the kidney, it may contribute to the detection of intraluminal pressure changes and urinary flow sensing. Acts as a shear stress sensor that promotes the organization and orientation of endothelial cells in the direction of blood flow by activating calpain.

The ion channel plays a key role in blood vessel formation and vascular structure in both development and adult physiology. Acts as a sensor for phosphatidylserine (PS) flip at the plasma membrane and controls muscle cell morphogenesis.

In myoblasts, flippase-mediated PS accumulation at the inner layer of the plasma membrane triggers channel activation and Ca2+ influx, followed by Rho-GTPase signaling leading to cortical actomyosin fiber formation and myotube formation (Tsuchiya M et al. 2018).

Diseases associated with PIEZO1 include dehydrated hereditary stomatocytosis 1 (hereditary stomatocytosis is a genetic hemolytic anemia caused by a structural defect in the erythrocytes) with or without pseudohyperkalemia and/or perinatal edema and lymphatic malformation .

1. Andolfo I et al. (2013) Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1. Blood 121:3925-35
2. Gnanasambandam R et al. (2015) Ionic Selectivity and Permeation Properties of Human PIEZO1 Channels. PLoS One 10:e0125503.
3. McHugh BJ et al. (2010) Integrin activation by Fam38A uses a novel mechanism of R-Ras targeting to the endoplasmic reticulum. J Cell Sci 123:51-61.
4. Tsuchiya M et al. (2018) Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-mediated myotube formation. Nat Commun 9:2049.