PIEZO1
Developmental stage
At 17 weeks of gestation, strongly expressed in hepatic erythroblasts. At that stage, also expressed in fetal splenic plasma cells and in lymphatic vessel of fetal peritoneum. In vitro, up-regulated during the erythroid differentiation of CD34+ cells from healthy donors (at protein level).
Function
Pore-forming subunit of a mechanosensitive non-specific cation Piezo channel (PubMed:23479567, PubMed:23695678, PubMed:25955826). Conductance to monovalent alkali ions is highest for K(+), intermediate for Na(+) and lowest for Li(+). Divalent ions except for Mn(2+) permeate the channel but more slowly than the monovalent ions and they also reduce K(+) currents (PubMed:25955826). Generates currents characterized by a linear current-voltage relationship that are sensitive to ruthenium red and gadolinium. Plays a key role in epithelial cell adhesion by maintaining integrin activation through R-Ras recruitment to the ER, most probably in its activated state, and subsequent stimulation of calpain signaling (PubMed:20016066). Piezo channels are homotrimeric three-blade propeller-shaped structure that utilize a cap-motion and plug-and-latch mechanism to gate their ion-conducting pathways (By similarity). In inner ear hair cells, PIEZO1/2 subunits may constitute part of the mechanotransducer (MET) non-selective cation channel complex where they may act as pore-forming ion-conducting component in the complex (By similarity). In the kidney, may contribute to the detection of intraluminal pressure changes and to urine flow sensing. Acts as a shear-stress sensor that promotes endothelial cell organization and alignment in the direction of blood flow through calpain activation (PubMed:25119035). Plays a key role in blood vessel formation and vascular structure in both development and adult physiology (By similarity). Acts as a sensor of phosphatidylserine (PS) flipping at the plasma membrane and governs morphogenesis of muscle cells. In myoblasts, flippase-mediated PS enrichment at the inner leaflet of plasma membrane triggers channel activation and Ca2+ influx followed by Rho GTPases signal transduction, leading to assembly of cortical actomyosin fibers and myotube formation (PubMed:29799007).
Involvement in disease
Dehydrated hereditary stomatocytosis 1 with or without pseudohyperkalemia and/or perinatal edema
DHS1
An autosomal dominant hemolytic anemia characterized by primary erythrocyte dehydration. DHS erythrocytes exhibit decreased total cation and potassium content that are not accompanied by a proportional net gain of sodium and water. DHS patients typically exhibit mild to moderate compensated hemolytic anemia, with an increased erythrocyte mean corpuscular hemoglobin concentration and a decreased osmotic fragility, both of which reflect cellular dehydration. Patients may also show perinatal edema and pseudohyperkalemia due to loss of potassium from red cells stored at room temperature. A minor proportion of red cells appear as stomatocytes on blood films. Complications such as splenomegaly and cholelithiasis, resulting from increased red cell trapping in the spleen and elevated bilirubin levels, respectively, may occur. The course of DHS is frequently associated with iron overload, which may lead to hepatosiderosis.
None
The disease is caused by variants affecting the gene represented in this entry. All disease-causing mutations characterized so far produce a gain-of-function phenotype, mutated channels exhibiting increased cation transport in erythroid cells, that could be due to slower channel inactivation rate compared to the wild-type protein.
Lymphatic malformation 6
LMPHM6
A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM6 is an autosomal recessive, severe form manifesting as generalized lymphatic dysplasia. It is characterized by uniform, widespread swelling of all segments of the body, with systemic involvement such as intestinal and/or pulmonary lymphangiectasia, pleural effusions, chylothoraces and/or pericardial effusions, and with a high incidence of non- immune hydrops fetalis.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the PIEZO (TC 1.A.75) family.
Tissue Specificity
Expressed in numerous tissues. In normal brain, expressed exclusively in neurons, not in astrocytes. In Alzheimer disease brains, expressed in about half of the activated astrocytes located around classical senile plaques. In Parkinson disease substantia nigra, not detected in melanin-containing neurons nor in activated astrocytes. Expressed in erythrocytes (at protein level). Expressed in myoblasts (at protein level).
Cellular localization
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- Endoplasmic reticulum-Golgi intermediate compartment membrane
- Cell membrane
- Multi-pass membrane protein
- Cell projection
- Lamellipodium membrane
- In erythrocytes, located in the plasma membrane (PubMed:22529292, PubMed:23479567). Accumulates at the leading apical lamellipodia of endothelial cells in response to shear stress (PubMed:25119035). Colocalizes with F-actin and MYH9 at the actomyosin cortex in myoblasts.
Alternative names
FAM38A, KIAA0233, PIEZO1, Piezo-type mechanosensitive ion channel component 1, Membrane protein induced by beta-amyloid treatment, Protein FAM38A, Mib