“PIEZO1”的意思、由来-开放百科全书

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.^[2]

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.^[1]

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.^[3]^[4]^[5] Piezo1 channels are pivotal integrators in vascular biology.^[6]

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.^[7]

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.^[8]

Ligands

References

1. ^¹{{cite journal | vauthors = Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, Dubin AE, Patapoutian A | title = Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels | journal = Science | volume = 330 | issue = 6000 | pages = 55–60 | date = October 2010 | pmid = 20813920 | pmc = 3062430 | doi = 10.1126/science.1193270 }}
2. ^{{cite journal | vauthors = Coste B, Xiao B, Santos JS, Syeda R, Grandl J, Spencer KS, Kim SE, Schmidt M, Mathur J, Dubin AE, Montal M, Patapoutian A | title = Piezo proteins are pore-forming subunits of mechanically activated channels | journal = Nature | volume = 483 | issue = 7388 | pages = 176–81 | date = March 2012 | pmid = 22343900 | pmc = 3297710 | doi = 10.1038/nature10812 }}
3. ^{{cite journal | vauthors = Zarychanski R, Schulz VP, Houston BL, Maksimova Y, Houston DS, Smith B, Rinehart J, Gallagher PG | title = Mutations in the mechanotransduction protein PIEZO1 are associated with hereditary xerocytosis | journal = Blood | volume = 120 | issue = 9 | pages = 1908–15 | date = August 2012 | pmid = 22529292 | doi = 10.1182/blood-2012-04-422253 | pmc=3448561}}
4. ^{{cite journal | vauthors = Bae C, Gnanasambandam R, Nicolai C, Sachs F, Gottlieb PA | title = Xerocytosis is caused by mutations that alter the kinetics of the mechanosensitive channel PIEZO1 | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 110 | issue = 12 | pages = E1162–8 | date = March 2013 | pmid = 23487776 | doi = 10.1073/pnas.1219777110 | pmc=3606986}}
5. ^{{cite journal | vauthors = Albuisson J, Murthy SE, Bandell M, Coste B, Louis-Dit-Picard H, Mathur J, Fénéant-Thibault M, Tertian G, de Jaureguiberry JP, Syfuss PY, Cahalan S, Garçon L, Toutain F, Simon Rohrlich P, Delaunay J, Picard V, Jeunemaitre X, Patapoutian A | title = Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels | journal = Nature Communications | volume = 4 | pages = 1884 | year = 2013 | pmid = 23695678 | doi = 10.1038/ncomms2899 | pmc=3674779}}
6. ^{{cite journal | vauthors = Li J, Hou B, Tumova S, Muraki K, Bruns A, Ludlow MJ, Sedo A, Hyman AJ, McKeown L, Young RS, Yuldasheva NY, Majeed Y, Wilson LA, Rode B, Bailey MA, Kim HR, Fu Z, Carter DA, Bilton J, Imrie H, Ajuh P, Dear TN, Cubbon RM, Kearney MT, Prasad KR, Evans PC, Ainscough JF, Beech DJ | display-authors = 6 | title = Piezo1 integration of vascular architecture with physiological force | journal = Nature | volume = 515 | issue = 7526 | pages = 279–82 | date = November 2014 | pmid = 25119035 | doi = 10.1038/nature13701 | pmc=4230887}}
7. ^{{cite journal | vauthors = Ma S, Cahalan S, LaMonte G, Grubaugh ND, Zeng W, Murthy SE, Paytas E, Gamini R, Lukacs V, Whitwam T, Loud M, Lohia R, Berry L, Khan SM, Janse CJ, Bandell M, Schmedt C, Wengelnik K, Su AI, Honore E, Winzeler EA, Andersen KG, Patapoutian A | title = Common PIEZO1 Allele in African Populations Causes RBC Dehydration and Attenuates Plasmodium Infection | journal = Cell | volume = 173 | issue = 2 | pages = 443–455.e12 | date = April 2018 | pmid = 29576450 | doi = 10.1016/j.cell.2018.02.047 }}
8. ^{{cite journal | vauthors = Eisenhoffer GT, Loftus PD, Yoshigi M, Otsuna H, Chien CB, Morcos PA, Rosenblatt J | title = Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia | journal = Nature | volume = 484 | issue = 7395 | pages = 546–9 | date = April 2012 | pmid = 22504183 | pmc = 4593481 | doi = 10.1038/nature10999 }}
9. ^{{cite journal | vauthors = Syeda R, Xu J, Dubin AE, Coste B, Mathur J, Huynh T, Matzen J, Lao J, Tully DC, Engels IH, Petrassi HM, Schumacher AM, Montal M, Bandell M, Patapoutian A | title = Chemical activation of the mechanotransduction channel Piezo1 | journal = eLife | volume = 4 | issue = | pages = | date = May 2015 | pmid = 26001275 | pmc = 4456433 | doi = 10.7554/eLife.07369 }}

Structure and function

Tissue distribution

Clinical significance

Ligands

References