PIEZO2 explained

Piezo-type mechanosensitive ion channel component 2 is a protein that in humans is encoded by the PIEZO2 gene.[1] 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.[2] It has a homotrimeric structure, with three blades curving into a nano-dome, with a diameter of 28 nanometers (nm).[3] 'Piezo' comes from the Greek 'piesi,' meaning 'pressure.'

Structure

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.[4] 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.[5] The three monomers meet in the center to form a ion-conducting pore across the membrane.[6] A cap-like domain sits on the extracellular side of the pore and may play a role in regulating ion flow. Each monomer of PIEZO2 has 38 transmembrane domains which is the most for any known protein in humans. 36 of these domains are located on the blade and every four form a repeated structure called a transmembrane helical unit or piezo repeat. 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. A 540 amino acid intracellular loop contains the latch, clasp, and beam domains of PIEZO2. The beam domain is 9 nm long and connects the blades with central pore region near the anchor region.

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. PIEZO2-mediated currents are responsive to both poke and stretch stimuli as measured by patch clamp electrophysiology.[7] PIEZO2 channels inactivate faster than PIEZO1 channels and can inactivate under continued mechanical stimulus. PIEZO2 has a single channel conductance between 20-30 picosiemens.

Physiological function

PIEZO2 has been implicated in a variety of physiological mechanoreceptive functions including touch, proprioception, nociception, and interoception.[8] PIEZO2 is expressed in sensory tissue such as sensory ganglia and epithelial cells in the bladder, colon, lungs, and stomach. For example, PIEZO2 is found in cell types that respond to physical touch, such as Merkel cells, and is thought to regulate light touch response.[9] 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 it can sense the pressure in the respiratory tract and play a role in the 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. It also plays role in skeletal and cartilage development and homeostasis, such as by detecting compression of chondrocytes.[10]

Pathology

See also

Further reading

Notes and References

  1. Web site: Entrez Gene: Piezo-type mechanosensitive ion channel component 2 . 2013-08-06 .
  2. 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 .
  3. 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 . 201116189 . 2019Natur.573..225W .
  4. Soattin L, Fiore M, Gavazzo P, Viti F, Facci P, Raiteri R, Difato F, Pusch M, Vassalli M . The biophysics of piezo1 and piezo2 mechanosensitive channels . Biophysical Chemistry . 208 . 26–33 . January 2016 . 26259784 . 10.1016/j.bpc.2015.06.013 . SIBPA 2014 - XXII SIBPA Congress .
  5. Jiang Y, Yang X, Jiang J, Xiao B . Structural Designs and Mechanogating Mechanisms of the Mechanosensitive Piezo Channels . Trends in Biochemical Sciences . 46 . 6 . 472–488 . June 2021 . 33610426 . 10.1016/j.tibs.2021.01.008 .
  6. Szczot M, Nickolls AR, Lam RM, Chesler AT . The Form and Function of PIEZO2 . Annual Review of Biochemistry . 90 . 90 . 507–534 . June 2021 . 34153212 . 8794004 . 10.1146/annurev-biochem-081720-023244 .
  7. 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 . 5407468 . 10.1016/j.tibs.2016.09.004 .
  8. Cheng Z, Wu Z, Wu M, Xie L, Chen Q . Piezo2 in Mechanosensory Biology: From Physiological Homeostasis to Disease-Promoting Mechanisms . Cell Proliferation . August 2025 . 40781923 . 10.1111/cpr.70112 . e70112 . free .
  9. Faucherre A, Nargeot J, Mangoni ME, Jopling C . piezo2b regulates vertebrate light touch response . The Journal of Neuroscience . 33 . 43 . 17089–17094 . October 2013 . 24155313 . 6618434 . 10.1523/jneurosci.0522-13.2013 . free .
  10. Qin L, He T, Chen S, Yang D, Yi W, Cao H, Xiao G . Roles of mechanosensitive channel Piezo1/2 proteins in skeleton and other tissues . Bone Research . 9 . 1 . 44 . October 2021 . 34667178 . 8526690 . 10.1038/s41413-021-00168-8 .
  11. 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 . 4667–4672 . March 2013 . 23487782 . 3607045 . 10.1073/pnas.1221400110 . free . 2013PNAS..110.4667C .
  12. 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 . 1756–1762 . December 2015 . 26551544 . 4661126 . 10.1038/nn.4162 .
  13. 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 . 734–744 . May 2014 . 24726473 . 4067551 . 10.1016/j.ajhg.2014.03.015 .

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