9vmx

Structural highlights

Disease

PIEZ1_HUMAN PIEZO1-related generalized lymphatic dysplasia with non-immune hydrops fetalis;Dehydrated hereditary stomatocytosis;Milroy disease. 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. The disease is caused by variants affecting the gene represented in this entry.

Function

PIEZ1_HUMAN 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).[UniProtKB:E2JF22][UniProtKB:Q91X60]^{[1] [2]}

References

1. ↑ Gnanasambandam R, Bae C, Gottlieb PA, Sachs F. Ionic Selectivity and Permeation Properties of Human PIEZO1 Channels. PLoS One. 2015 May 8;10(5):e0125503. PMID:25955826 doi:10.1371/journal.pone.0125503
2. ↑ Tsuchiya M, Hara Y, Okuda M, Itoh K, Nishioka R, Shiomi A, Nagao K, Mori M, Mori Y, Ikenouchi J, Suzuki R, Tanaka M, Ohwada T, Aoki J, Kanagawa M, Toda T, Nagata Y, Matsuda R, Takayama Y, Tominaga M, Umeda M. Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-mediated myotube formation. Nat Commun. 2018 May 24;9(1):2049. PMID:29799007 doi:10.1038/s41467-018-04436-w