PIEZO1

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
Identifiers
Aliases	PIEZO1, DHS, FAM38A, Mib, LMPH3, piezo type mechanosensitive ion channel component 1, LMPHM6
External IDs	OMIM: 611184 MGI: 3603204 HomoloGene: 124356 GeneCards: PIEZO1
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16q24.3 Start 88,715,338 bp[1] End 88,785,220 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 E1 Start 122,481,698 bp[2] End 122,551,329 bp[2]
Gene ontology Molecular function • cation channel activity • mechanically-gated ion channel activity Cellular component • integral component of membrane • cell projection • endoplasmic reticulum-Golgi intermediate compartment membrane • endoplasmic reticulum membrane • endoplasmic reticulum • lamellipodium membrane • membrane • cell membrane Biological process • ion transmembrane transport • positive regulation of cell-cell adhesion mediated by integrin • cation transport • positive regulation of integrin activation • ion transport • cation transmembrane transport • regulation of membrane potential • detection of mechanical stimulus • cellular response to mechanical stimulus • transmembrane transport Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	9780	234839
Ensembl	ENSG00000103335	ENSMUSG00000014444
UniProt	Q92508	E2JF22
RefSeq (mRNA)	NM_001142864	NM_001037298 NM_001357349
RefSeq (protein)	NP_001136336	n/a
Location (UCSC)	Chr 16: 88.72 – 88.79 Mb	Chr 8: 122.48 – 122.55 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Structure and function

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]

It is assumed that Piezo1 channel is a three-bladed propeller-like structure and a lever-like mechanogating mechanism.[7][8]

Tissue distribution

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]

Clinical significance

Piezo1 is also found in red blood cells, and gain of function mutations in the channels are associated with hereditary xerocytosis or stomatocytosis.[9][10][11] Piezo1 channels are pivotal integrators in vascular biology.[12]

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.[13]

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.[14]

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.[15]

Ligands

Agonists

• Yoda1 (small molecule agonist)[16]

References

1. GRCh38: Ensembl release 89: ENSG00000103335 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000014444 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, et al. (October 2010). "Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels". Science. 330 (6000): 55–60. Bibcode:2010Sci...330...55C. doi:10.1126/science.1193270. PMC 3062430. PMID 20813920.
6. Coste B, Xiao B, Santos JS, Syeda R, Grandl J, Spencer KS, et al. (February 2012). "Piezo proteins are pore-forming subunits of mechanically activated channels". Nature. 483 (7388): 176–81. Bibcode:2012Natur.483..176C. doi:10.1038/nature10812. PMC 3297710. PMID 22343900.
7. 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.
8. 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. PMC 5880808. PMID 29610524.
9. 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): 1908–15. doi:10.1182/blood-2012-04-422253. PMC 3448561. PMID 22529292.
10. 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): E1162-8. Bibcode:2013PNAS..110E1162B. doi:10.1073/pnas.1219777110. PMC 3606986. PMID 23487776.
11. 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. PMC 3674779. PMID 23695678.
12. 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. PMC 4230887. PMID 25119035.
13. 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. PMC 5889333. PMID 29576450.
14. 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): 546–9. Bibcode:2012Natur.484..546E. doi:10.1038/nature10999. PMC 4593481. PMID 22504183.
15. 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. PMC 6939392. PMID 31435009.
16. 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. PMC 4456433. PMID 26001275.