PIEZO2

PIEZO2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 6KG7
Identifiers
Aliases	PIEZO2 , C18orf30, C18orf58, DA3, DA5, FAM38B, FAM38B2, HsT748, HsT771, MWKS, piezo type mechanosensitive ion channel component 2, DAIPT
External IDs	OMIM: 613629; MGI: 1918781; HomoloGene: 49695; GeneCards: PIEZO2; OMA:PIEZO2 - orthologs
Gene location (Human) Chr. Chromosome 18 (human) [1] Band 18p11.22-p11.21 Start 10,666,483 bp [1] End 11,149,569 bp [1]
Gene location (Mouse) Chr. Chromosome 18 (mouse) [2] Band 18|18 E1 Start 63,143,284 bp [2] End 63,520,254 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in sural nerve corpus callosum spinal ganglia visceral pleura inferior ganglion of vagus nerve trigeminal ganglion parietal pleura optic nerve C1 segment Achilles tendon Top expressed in lumbar spinal ganglion prostate lobe of prostate cumulus cell trigeminal ganglion genital tubercle hand aortic valve ascending aorta gastrula More reference expression data BioGPS n/a
Gene ontology Molecular function cation channel activity mechanosensitive ion channel activity Cellular component membrane integral component of membrane plasma membrane Biological process ion transmembrane transport response to mechanical stimulus ion transport response to stimulus cation transport detection of mechanical stimulus involved in sensory perception regulation of membrane potential detection of mechanical stimulus cellular response to mechanical stimulus cation transmembrane transport transmembrane transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 63895 667742 Ensembl ENSG00000154864 ENSMUSG00000041482 UniProt Q9H5I5 Q8CD54 RefSeq (mRNA) NM_022068 NM_173817 NM_001378183 NM_001039485 NM_172629 RefSeq (protein) NP_071351 NP_001365112 NP_001034574 Location (UCSC) Chr 18: 10.67 – 11.15 Mb Chr 18: 63.14 – 63.52 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Piezo-type mechanosensitive ion channel component 2 is a protein that in humans is encoded by the PIEZO2 gene. ^[5] The PIEZO2 protein has a role in mechanotransduction. Mechanical activation of the channel leads to depolarization of the plasma membrane or activation of secondary messenger cascades. PIEZO2 was cloned in 2010 after its homolog, PIEZO1, was identified using small interfering RNAs of candidate genes for mechanically activated ion channels in mouse neurons. ^[6] It has a homotrimeric structure, with three blades curving into a nano-dome, with a diameter of 28 nanometers (nm). ^[7] 'Piezo' comes from the Greek 'piesi,' meaning 'pressure.'

Structure

Diagram demonstrating structural components of the PIEZO2 complex, the nano-dome shape in the closed state, and how mechanical stimuli open the channel to allow ion flow.

Piezos are large transmembrane proteins conserved among various species, but they don't have known sequence similarity to any other class of proteins. Piezo proteins contain around 2500-2800 amino acids depending on the species. ^[8] The structure of piezo proteins has been determined using cryo-electron microscopy. They have a homotrimeric propellor-like structure composed on three blades curved into a nano-dome with a diameter of 28 nm and axial height of 17 nm. ^{[7] [9]} The three monomers meet in the center to form a ion-conducting pore across the membrane. ^[10] A cap-like domain sits on the extracellular side of the pore and may play a role in regulating ion flow. ^[9] Each monomer of PIEZO2 has 38 transmembrane domains which is the most for any known protein in humans. ^[10] 36 of these domains are located on the blade and every four form a repeated structure called a transmembrane helical unit or piezo repeat. ^[9] The blades form a nano-dome shape which deform the local curvature of the membrane. Under lateral tension from the lipids and changes to the local curvature of the membrane, the dome can be reversibly flattened which is how it is proposed to detect mechanical stimuli. ^{[9] [10]} A 540 amino acid intracellular loop contains the latch, clasp, and beam domains of PIEZO2. ^[7] The beam domain is 9 nm long and connects the blades with central pore region near the anchor region. ^[9]

Function

See also: Mechanosensitive channels and Somatosensory system

Molecular function

PIEZO2 is a mechanically activated cation channel. PIEZO2 produces an excitatory current by nonselective conduction of cations through the central pore, slightly preferring calcium. The influx of cations depolarizes the plasma membrane and can activate secondary messenger cascades. ^[10] PIEZO2-mediated currents are responsive to both poke and stretch stimuli as measured by patch clamp electrophysiology. ^[11] PIEZO2 channels inactivate faster than PIEZO1 channels and can inactivate under continued mechanical stimulus. ^[8] PIEZO2 has a single channel conductance between 20-30 picosiemens. ^[8]

Physiological function

PIEZO2 has been implicated in a variety of physiological mechanoreceptive functions including touch, proprioception, nociception, and interoception. ^{[10] [12]} PIEZO2 is expressed in sensory tissue such as sensory ganglia and epithelial cells in the bladder, colon, lungs, and stomach. ^{[6] [10]} For example, PIEZO2 is found in cell types that respond to physical touch, such as Merkel cells, ^[11] and is thought to regulate light touch response. ^[13] In the gastrointestinal tract, PIEZO2 is expressed in enteroendocrine cells, where it can signal intestinal stretch and is involved in the release of neurotransmitters and hormones. PIEZO2 is expressed in the neuroepithelial cells of the lungs where is can sense the pressure in the respiratory tract and play a role regulation of breathing. In the urinary system, PIEZO2 is the primary mechanoreceptor for innervation of the bladder at low pressures. Along with PIEZO1, PIEZO2 plays a role regulating blood pressure through the baroreflex. ^[10] It also plays role in skeletal and cartilage development and homeostasis, such as by detecting compression of chondrocytes. ^[14]

Pathology

• Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis. ^[15]
• Mice without PIEZO2 in their proprioceptive neurons show uncoordinated body movements, indicating that PIEZO2 plays a role in mammalian proprioception. ^[16]
• PIEZO2 mutations link Gordon syndrome (distal arthrogryposis type 3), Marden-Walker syndrome and Arthrogryposis (Distal Arthrogryposis Type 5). ^[17]
• Loss of function mutations result in severe loss of proprioception, insensitivity to touch and vibration, perinatal respiratory distress, and motor and skeletal abnormalities. ^{[10] [16]}

See also

• PIEZO1

References

1. GRCh38: Ensembl release 89: ENSG00000154864 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000041482 – 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. "Entrez Gene: Piezo-type mechanosensitive ion channel component 2" . Retrieved 2013-08-06.
6. 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.
7. Wang L, Zhou H, Zhang M, Liu W, Deng T, Zhao Q, et al. (September 2019). "Structure and mechanogating of the mammalian tactile channel PIEZO2". Nature. 573 (7773): 225–229. Bibcode:2019Natur.573..225W. doi:10.1038/s41586-019-1505-8. PMID   31435011. S2CID   201116189.
8. Soattin L, Fiore M, Gavazzo P, Viti F, Facci P, Raiteri R, et al. (1 Jan 2016). "The biophysics of piezo1 and piezo2 mechanosensitive channels". Biophysical Chemistry. SIBPA 2014 - XXII SIBPA Congress. 208: 26–33. doi:10.1016/j.bpc.2015.06.013. ISSN   0301-4622.
9. Jiang Y, Yang X, Jiang J, Xiao B (Jun 2021). "Structural Designs and Mechanogating Mechanisms of the Mechanosensitive Piezo Channels". Trends in Biochemical Sciences. 46 (6): 472–488. doi:10.1016/j.tibs.2021.01.008.
10. Szczot M, Nickolls AR, Lam RM, Chesler AT (20 Jun 2021). "The Form and Function of PIEZO2". Annual Review of Biochemistry. 90 (90): 507–534. doi:10.1146/annurev-biochem-081720-023244. ISSN   0066-4154. PMC   8794004 . PMID   34153212.
11. Wu J, Lewis AH, Grandl J (Jan 2017). "Touch, Tension, and Transduction – The Function and Regulation of Piezo Ion Channels". Trends in Biochemical Sciences. 42 (1): 57–71. doi:10.1016/j.tibs.2016.09.004. PMC   5407468 . PMID   27743844.
12. Cheng Z, Wu Z, Wu M, Xie L, Chen Q. "Piezo2 in Mechanosensory Biology: From Physiological Homeostasis to Disease-Promoting Mechanisms". Cell Proliferation e70112. doi:10.1111/cpr.70112. ISSN   1365-2184.
13. Faucherre A, Nargeot J, Mangoni ME, Jopling C (October 2013). "piezo2b regulates vertebrate light touch response". The Journal of Neuroscience. 33 (43): 17089–94. doi: 10.1523/jneurosci.0522-13.2013 . PMC   6618434 . PMID   24155313.
14. Qin L, He T, Chen S, Yang D, Yi W, Cao H, et al. (2021-10-20). "Roles of mechanosensitive channel Piezo1/2 proteins in skeleton and other tissues". Bone Research. 9 (1): 44. doi:10.1038/s41413-021-00168-8. ISSN   2095-6231. PMC   8526690 . PMID   34667178.
15. Coste B, Houge G, Murray MF, Stitziel N, Bandell M, Giovanni MA, et al. (March 2013). "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. Bibcode:2013PNAS..110.4667C. doi: 10.1073/pnas.1221400110 . PMC   3607045 . PMID   23487782.
16. Woo SH, Lukacs V, de Nooij JC, Zaytseva D, Criddle CR, Francisco A, et al. (December 2015). "Piezo2 is the principal mechanotransduction channel for proprioception". Nature Neuroscience. 18 (12): 1756–62. doi:10.1038/nn.4162. PMC   4661126 . PMID   26551544.
17. McMillin MJ, Beck AE, Chong JX, Shively KM, Buckingham KJ, Gildersleeve HI, et al. (May 2014). "Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5". American Journal of Human Genetics. 94 (5): 734–44. doi:10.1016/j.ajhg.2014.03.015. PMC   4067551 . PMID   24726473.

Further reading

• Uher R, Tansey KE, Henigsberg N, Wolfgang M, Mors O, Hauser J, et al. (GENDEP Investigators; MARS Investigators; STAR*D Investigators) (February 2013). "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. doi:10.1176/appi.ajp.2012.12020237. PMC   10416089 . PMID   23377640.
• Ahn MJ, Won HH, Lee J, Lee ST, Sun JM, Park YH, et al. (March 2012). "The 18p11.22 locus is associated with never smoker non-small cell lung cancer susceptibility in Korean populations". Human Genetics. 131 (3): 365–72. doi:10.1007/s00439-011-1080-z. PMID   21866343. S2CID   16395362.
• Del-Aguila JL, Beitelshees AL, Cooper-Dehoff RM, Chapman AB, Gums JG, Bailey K, et al. (February 2014). "Genome-wide association analyses suggest NELL1 influences adverse metabolic response to HCTZ in African Americans". The Pharmacogenomics Journal. 14 (1): 35–40. doi:10.1038/tpj.2013.3. PMC   3812324 . PMID   23400010.
• Coste B, Houge G, Murray MF, Stitziel N, Bandell M, Giovanni MA, et al. (March 2013). "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. Bibcode:2013PNAS..110.4667C. doi: 10.1073/pnas.1221400110 . PMC   3607045 . PMID   23487782.
• Wang X, Shaffer JR, Zeng Z, Begum F, Vieira AR, Noel J, et al. (December 2012). "Genome-wide association scan of dental caries in the permanent dentition". BMC Oral Health. 12: 57. doi: 10.1186/1472-6831-12-57 . PMC   3574042 . PMID   23259602.
• Xiao R, Xu XZ (November 2010). "Mechanosensitive channels: in touch with Piezo". Current Biology. 20 (21): R936-8. Bibcode:2010CBio...20.R936X. doi:10.1016/j.cub.2010.09.053. PMC   3018681 . PMID   21056836.
• Coste B (January 2011). "[Feeling the pressure? Identification of two proteins activated by mechanical forces]". Médecine/Sciences. 27 (1): 17–9. doi: 10.1051/medsci/201127117 . PMID   21299953.
• Dubin AE, Schmidt M, Mathur J, Petrus MJ, Xiao B, Coste B, et al. (September 2012). "Inflammatory signals enhance piezo2-mediated mechanosensitive currents". Cell Reports. 2 (3): 511–7. doi:10.1016/j.celrep.2012.07.014. PMC   3462303 . PMID   22921401.
• Luykx JJ, Bakker SC, Lentjes E, Neeleman M, Strengman E, Mentink L, et al. (February 2014). "Genome-wide association study of monoamine metabolite levels in human cerebrospinal fluid". Molecular Psychiatry. 19 (2): 228–34. doi: 10.1038/mp.2012.183 . PMID   23319000. S2CID   8713026.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.