PIEZO1 is a mechanosensitive ion channel protein that in humans is encoded by the gene PIEZO1. PIEZO1 and its close homolog PIEZO2 were cloned in 2010, using an siRNA-based screen for mechanosensitive ion channels.[5]
PIEZO1 (this gene) and PIEZO2 share 47% identity with each other and they have no similarity to any other protein and contain no known protein domains. They are predicted to have 24-36 transmembrane domains, depending on the prediction algorithm used. In the original publication the authors were careful not to call the piezo proteins ion channels, but a more recent study by the same lab convincingly demonstrated that indeed PIEZO1 is the pore-forming subunit of a mechanosensitive channel.[6] This new " PIEZO" family is catalogued as InterPro: IPR027272 and TCDB1.A.75. PIEZO1 homologues are found in C. elegans and Drosophila, which, like other invertebrates, have a single PIEZO protein.
It is known (PDB: 6B3R) that PIEZO1 channel is a three-bladed propeller-like structure. A lever-like mechanogating mechanism is assumed.[7][8]
Tissue distributionedit
PIEZO1 is expressed in the lungs, bladder and skin, where mechanosensation has important biological roles. Unlike PIEZO2 which is highly expressed in sensory dorsal root ganglia, PIEZO1 is not expressed in sensory neurons.[5] Consequently PIEZO1 plays a significant role in multiple neurobiological processes including axon regeneration, neural stem cells differentiation and neurological diseases progression.[9]
An allele of PIEZO1, E756del, results in a gain-of-function mutation, resulting in dehydrated RBCs and conveying resistance to Plasmodium. This allele has been demonstrated in vitro to prevent cerebral malaria infection.[14]
PIEZO1 has been implicated in extrusion of epidermal cells when a layer becomes too confluent to preserve normal skin homeostasis. This acts to prevent excess proliferation of skin tissue, and has been implicated in cancer biology as a contributing factor to metastases by assisting living cells in escaping from a monolayer.[15]
Expression of murine PIEZO1 in mouse innate immune cells is essential for their function, a role mediated by sensing mechanical cues. Deficiency in PIEZO1 in mice lead to increased susceptibility of myeloid cells to infection by Pseudomonas aeruginosa.[16]
PIEZO1 has been proposed as a therapeutic target for Alzheimer's disease. The build-up of amyloid-β plaques which stiffens the brain's structure. Microglial maintenance cells, which express PIEZO1, detect this stiffness via PIEZO1-enabled mechanosensation and in response surround, compact, and phagocytosize the plaques. Removal of the gene which codes for PIEZO1 in microglia decreases plaque clearance and hastens cognitive decline in rats.[18]
^Zhao Q, Zhou H, Li X, Xiao B (July 2019). "The mechanosensitive Piezo1 channel: a three-bladed propeller-like structure and a lever-like mechanogating mechanism". The FEBS Journal. 286 (13): 2461–2470. doi:10.1111/febs.14711. PMID 30500111.
^Wang Y, Chi S, Guo H, Li G, Wang L, Zhao Q, et al. (April 2018). "A lever-like transduction pathway for long-distance chemical- and mechano-gating of the mechanosensitive Piezo1 channel". Nature Communications. 9 (1): 1300. Bibcode:2018NatCo...9.1300W. doi:10.1038/s41467-018-03570-9. PMC5880808. PMID 29610524.
^Bryniarska-Kubiak N, Kubiak A, Basta-Kaim A (October 2023). "Mechanotransductive Receptor Piezo1 as a Promising Target in the Treatment of Neurological Diseases". Current Neuropharmacology. 21 (10): 2030–2035. doi:10.2174/1570159X20666220927103454. PMC10556366. PMID 36173070.
^Zarychanski R, Schulz VP, Houston BL, Maksimova Y, Houston DS, Smith B, et al. (August 2012). "Mutations in the mechanotransduction protein PIEZO1 are associated with hereditary xerocytosis". Blood. 120 (9): 1908–1915. doi:10.1182/blood-2012-04-422253. PMC3448561. PMID 22529292.
^Bae C, Gnanasambandam R, Nicolai C, Sachs F, Gottlieb PA (March 2013). "Xerocytosis is caused by mutations that alter the kinetics of the mechanosensitive channel PIEZO1". Proceedings of the National Academy of Sciences of the United States of America. 110 (12): E1162–E1168. Bibcode:2013PNAS..110E1162B. doi:10.1073/pnas.1219777110. PMC3606986. PMID 23487776.
^Albuisson J, Murthy SE, Bandell M, Coste B, Louis-Dit-Picard H, Mathur J, et al. (2013). "Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels". Nature Communications. 4: 1884. Bibcode:2013NatCo...4.1884A. doi:10.1038/ncomms2899. PMC3674779. PMID 23695678.
^Li J, Hou B, Tumova S, Muraki K, Bruns A, Ludlow MJ, et al. (November 2014). "Piezo1 integration of vascular architecture with physiological force". Nature. 515 (7526): 279–282. Bibcode:2014Natur.515..279L. doi:10.1038/nature13701. PMC4230887. PMID 25119035.
^Ma S, Cahalan S, LaMonte G, Grubaugh ND, Zeng W, Murthy SE, et al. (April 2018). "Common PIEZO1 Allele in African Populations Causes RBC Dehydration and Attenuates Plasmodium Infection". Cell. 173 (2): 443–455.e12. doi:10.1016/j.cell.2018.02.047. PMC5889333. PMID 29576450.
^Eisenhoffer GT, Loftus PD, Yoshigi M, Otsuna H, Chien CB, Morcos PA, Rosenblatt J (April 2012). "Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia". Nature. 484 (7395): 546–549. Bibcode:2012Natur.484..546E. doi:10.1038/nature10999. PMC4593481. PMID 22504183.
^Solis AG, Bielecki P, Steach HR, Sharma L, Harman CC, Yun S, et al. (September 2019). "Mechanosensation of cyclical force by PIEZO1 is essential for innate immunity". Nature. 573 (7772): 69–74. Bibcode:2019Natur.573...69S. doi:10.1038/s41586-019-1485-8. PMC6939392. PMID 31435009.
^Fotiou E, Martin-Almedina S, Simpson MA, Lin S, Gordon K, Brice G, et al. (September 2015). "Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis". Nature Communications. 6: 8085. Bibcode:2015NatCo...6.8085F. doi:10.1038/ncomms9085. PMC4568316. PMID 26333996.
^Hu J, Chen Q, Zhu H, Hou L, Liu W, Yang Q, Shen H, Chai G, Zhang B, Chen S, Cai Z, Wu C, Hong F, Li H, Chen S (January 2023). "Microglial Piezo1 senses Aβ fibril stiffness to restrict Alzheimer's disease". Neuron. 111 (1): 15–29.e8. doi:10.1016/j.neuron.2022.10.021. ISSN 0896-6273. PMID 36368316.
^Syeda R, Xu J, Dubin AE, Coste B, Mathur J, Huynh T, et al. (May 2015). "Chemical activation of the mechanotransduction channel Piezo1". eLife. 4. doi:10.7554/eLife.07369. PMC4456433. PMID 26001275.
^Bae C, Sachs F, Gottlieb PA (2011-07-26). "The mechanosensitive ion channel Piezo1 is inhibited by the peptide GsMTx4". Biochemistry. 50 (29): 6295–6300. doi:10.1021/bi200770q. ISSN 0006-2960. PMC3169095. PMID 21696149.