PIEZO2 explained

Piezo-type mechanosensitive ion channel component 2 is a protein that in humans is encoded by the PIEZO2 gene.^[1] It has a homotrimeric structure, with three blades curving into a nano-dome, with a diameter of 28 nanometers.^[2]

Function

See also: Mechanosensitive channels and Somatosensory system. Piezos are large transmembrane proteins conserved among various species, all having between 24 and 36 predicted transmembrane domains. 'Piezo' comes from the Greek 'piesi,' meaning 'pressure.' The PIEZO2 protein has a role in rapidly adapting mechanically activated (MA) currents in somatosensory neurons.^[3] Its structure is resolved via a mouse version in 2019, showing the predicted homotrimeric propeller.^[4]

PIEZO2 is typically found in cell types that respond to physical touch, such as Merkel cells,^[5] and is thought to regulate light touch response.^[6]

Pathology

• Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis.^[7]
• Mice without PIEZO2 in their proprioceptive neurons show uncoordinated body movements, indicating that PIEZO2 plays a role in mammalian proprioception.^[8]
• PIEZO2 mutations link Gordon syndrome (distal arthrogryposis type 3), Marden-Walker syndrome and Arthrogryposis (Distal Arthrogryposis Type 5).^[9]

See also

• PIEZO1

Further reading

• Uher R, Tansey KE, Henigsberg N, Wolfgang M, Mors O, Hauser J . GENDEP Investigators; MARS Investigators; STAR*D Investigators . Common genetic variation and antidepressant efficacy in major depressive disorder: a meta-analysis of three genome-wide pharmacogenetic studies . The American Journal of Psychiatry . 170 . 2 . 207–17 . February 2013 . 23377640 . 10.1176/appi.ajp.2012.12020237 . 10416089 .
• Ahn MJ, Won HH, Lee J, Lee ST, Sun JM, Park YH, Ahn JS, Kwon OJ, Kim H, Shim YM, Kim J, Kim K, Kim YH, Park JY, Kim JW, Park K . The 18p11.22 locus is associated with never smoker non-small cell lung cancer susceptibility in Korean populations . Human Genetics . 131 . 3 . 365–72 . March 2012 . 21866343 . 10.1007/s00439-011-1080-z . 16395362 .
• Del-Aguila JL, Beitelshees AL, Cooper-Dehoff RM, Chapman AB, Gums JG, Bailey K, Gong Y, Turner ST, Johnson JA, Boerwinkle E . Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans . The Pharmacogenomics Journal . 14 . 1 . 35–40 . February 2014 . 23400010 . 3812324 . 10.1038/tpj.2013.3 .
• Coste B, Houge G, Murray MF, Stitziel N, Bandell M, Giovanni MA, Philippakis A, Hoischen A, Riemer G, Steen U, Steen VM, Mathur J, Cox J, Lebo M, Rehm H, Weiss ST, Wood JN, Maas RL, Sunyaev SR, Patapoutian A . Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis . Proceedings of the National Academy of Sciences of the United States of America . 110 . 12 . 4667–72 . March 2013 . 23487782 . 3607045 . 10.1073/pnas.1221400110 . 2013PNAS..110.4667C . free .
• Wang X, Shaffer JR, Zeng Z, Begum F, Vieira AR, Noel J, Anjomshoaa I, Cuenco KT, Lee MK, Beck J, Boerwinkle E, Cornelis MC, Hu FB, Crosslin DR, Laurie CC, Nelson SC, Doheny KF, Pugh EW, Polk DE, Weyant RJ, Crout R, McNeil DW, Weeks DE, Feingold E, Marazita ML . Genome-wide association scan of dental caries in the permanent dentition . BMC Oral Health . 12 . 57 . December 2012 . 23259602 . 3574042 . 10.1186/1472-6831-12-57 . free .
• Xiao R, Xu XZ . Mechanosensitive channels: in touch with Piezo . Current Biology . 20 . 21 . R936-8 . November 2010 . 21056836 . 3018681 . 10.1016/j.cub.2010.09.053 . 2010CBio...20.R936X .
• Coste B . [Feeling the pressure? Identification of two proteins activated by mechanical forces] . Médecine/Sciences . 27 . 1 . 17–9 . January 2011 . 21299953 . 10.1051/medsci/201127117 . free .
• Dubin AE, Schmidt M, Mathur J, Petrus MJ, Xiao B, Coste B, Patapoutian A . Inflammatory signals enhance piezo2-mediated mechanosensitive currents . Cell Reports . 2 . 3 . 511–7 . September 2012 . 22921401 . 3462303 . 10.1016/j.celrep.2012.07.014 .
• Luykx JJ, Bakker SC, Lentjes E, Neeleman M, Strengman E, Mentink L, DeYoung J, de Jong S, Sul JH, Eskin E, van Eijk K, van Setten J, Buizer-Voskamp JE, Cantor RM, Lu A, van Amerongen M, van Dongen EP, Keijzers P, Kappen T, Borgdorff P, Bruins P, Derks EM, Kahn RS, Ophoff RA . Genome-wide association study of monoamine metabolite levels in human cerebrospinal fluid . Molecular Psychiatry . 19 . 2 . 228–34 . February 2014 . 23319000 . 10.1038/mp.2012.183 . 8713026 . free .

Notes and References

1. Web site: Entrez Gene: Piezo-type mechanosensitive ion channel component 2. 2013-08-06 .
2. Wang L, Zhou H, Zhang M, Liu W, Deng T, Zhao Q, Li Y, Lei J, Li X, Xiao B . Structure and mechanogating of the mammalian tactile channel PIEZO2 . Nature . 573 . 7773 . 225–229 . September 2019 . 31435011 . 10.1038/s41586-019-1505-8 . 2019Natur.573..225W . 201116189 .
3. Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, Dubin AE, Patapoutian A . Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels . Science . 330 . 6000 . 55–60 . October 2010 . 20813920 . 3062430 . 10.1126/science.1193270 . 2010Sci...330...55C .
4. Wang L, Zhou H, Zhang M, Liu W, Deng T, Zhao Q, Li Y, Lei J, Li X, Xiao B . Structure and mechanogating of the mammalian tactile channel PIEZO2 . Nature . 573 . 7773 . 225–229 . September 2019 . 31435011 . 10.1038/s41586-019-1505-8 . 2019Natur.573..225W . 201116189 .
5. Wu J, Lewis AH, Grandl J . Touch, Tension, and Transduction - The Function and Regulation of Piezo Ion Channels . Trends in Biochemical Sciences . 42 . 1 . 57–71 . January 2017 . 27743844 . 10.1016/j.tibs.2016.09.004 . 5407468 .
6. Faucherre A, Nargeot J, Mangoni ME, Jopling C . piezo2b regulates vertebrate light touch response . The Journal of Neuroscience . 33 . 43 . 17089–94 . October 2013 . 24155313 . 10.1523/jneurosci.0522-13.2013 . 6618434 . free .
7. Coste B, Houge G, Murray MF, Stitziel N, Bandell M, Giovanni MA, Philippakis A, Hoischen A, Riemer G, Steen U, Steen VM, Mathur J, Cox J, Lebo M, Rehm H, Weiss ST, Wood JN, Maas RL, Sunyaev SR, Patapoutian A . Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis . Proceedings of the National Academy of Sciences of the United States of America . 110 . 12 . 4667–72 . March 2013 . 23487782 . 3607045 . 10.1073/pnas.1221400110 . 2013PNAS..110.4667C . free .
8. Woo SH, Lukacs V, de Nooij JC, Zaytseva D, Criddle CR, Francisco A, Jessell TM, Wilkinson KA, Patapoutian A . Piezo2 is the principal mechanotransduction channel for proprioception . Nature Neuroscience . 18 . 12 . 1756–62 . December 2015 . 26551544 . 10.1038/nn.4162 . 4661126 .
9. McMillin MJ, Beck AE, Chong JX, Shively KM, Buckingham KJ, Gildersleeve HI, Aracena MI, Aylsworth AS, Bitoun P, Carey JC, Clericuzio CL, Crow YJ, Curry CJ, Devriendt K, Everman DB, Fryer A, Gibson K, Giovannucci Uzielli ML, Graham JM, Hall JG, Hecht JT, Heidenreich RA, Hurst JA, Irani S, Krapels IP, Leroy JG, Mowat D, Plant GT, Robertson SP, Schorry EK, Scott RH, Seaver LH, Sherr E, Splitt M, Stewart H, Stumpel C, Temel SG, Weaver DD, Whiteford M, Williams MS, Tabor HK, Smith JD, Shendure J, Nickerson DA, Bamshad MJ . Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5 . American Journal of Human Genetics . 94 . 5 . 734–44 . May 2014 . 24726473 . 4067551 . 10.1016/j.ajhg.2014.03.015 .