Pore-forming subunit of a mechanosensitive non-specific cation channel (, ). 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 . 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 . 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.
Subcellular locations: Endoplasmic reticulum membrane, Endoplasmic reticulum-Golgi intermediate compartment membrane, Cell membrane, Cell projection, Lamellipodium membrane, Cell membrane
In erythrocytes, located in the plasma membrane (, ). Accumulates at the leading apical lamellipodia of endothelial cells in response to shear stress . Colocalizes with F-actin and MYH9 at the actomyosin cortex in myoblasts.
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).