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Piezos thrive under pressure: mechanically activated ion channels in health and disease

Nature Reviews Molecular Cell Biology volume 18, pages 771–783 (2017)Cite this article

Subjects

Key Points

  • Piezos are bona fide mechanically activated ion channels that have a leading role in several cellular mechanotransduction events.

  • Piezo proteins are unique in their size and lack homology to other membrane proteins. However, recent structural and functional studies have started to unravel architectural features of the channel.

  • Piezo ion channels are activated by various physiologically relevant physical forces.

  • The Piezo1 channel is involved in cardiovascular mechanotransduction, red blood cell volume regulation and epithelial homeostasis, and the Piezo2 channel is involved in sensory and respiratory mechanotransduction.

  • Several genetic disorders linked to mutations in PIEZO1 and PIEZO2 have helped to uncover unexpected roles for mechanotransduction in mammalian physiology.

Abstract

Cellular mechanotransduction, the process of translating mechanical forces into biological signals, is crucial for a wide range of physiological processes. A role for ion channels in sensing mechanical forces has been proposed for decades, but their identity in mammals remained largely elusive until the discovery of Piezos. Recent research on Piezos has underscored their importance in somatosensation (touch perception, proprioception and pulmonary respiration), red blood cell volume regulation, vascular physiology and various human genetic disorders.

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Figure 1: Topology and structural orientation of Piezo1.
Figure 2: Models of activation for Piezo channels.
Figure 3: Physiological role of Piezo channels.

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References

  1. Corey, D. P. & Hudspeth, A. J. Response latency of vertebrate hair cells. Biophys. J. 26, 499–506 (1979).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. Guharay, F. & Sachs, F. Stretch-activated single ion channel currents in tissue-cultured embryonic chick skeletal muscle. J. Physiol. 352, 685–701 (1984).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Katta, S., Krieg, M. & Goodman, M. B. Feeling force: physical and physiological principles enabling sensory mechanotransduction. Annu. Rev. Cell Dev. Biol. 31, 347–371 (2015).

    Article  PubMed  CAS  Google Scholar 

  4. Morris, C. E., Prikryl, E. A. & Joós, B. Mechanosensitive gating of Kv channels. PLoS ONE 10, e0118335 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  5. Delmas, P., Hao, J. & Rodat-Despoix, L. Molecular mechanisms of mechanotransduction in mammalian sensory neurons. Nat. Rev. Neurosci. 12, 139–153 (2011).

    Article  PubMed  CAS  Google Scholar 

  6. Coste, B. et al. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 330, 55–60 (2010). This study reports the identification of Piezos.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Holle, A. W. & Engler, A. J. More than a feeling: discovering, understanding, and influencing mechanosensing pathways. Curr. Opin. Biotechnol. 22, 648–654 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Ranade, S. S., Syeda, R. & Patapoutian, A. Mechanically activated ion channels. Neuron 87, 1162–1179 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Sun, Z., Guo, S. S. & Fässler, R. Integrin-mediated mechanotransduction. J. Cell Biol. 215, 445–456 (2016).

    PubMed  PubMed Central  CAS  Google Scholar 

  10. Honoré, E., Martins, J. R., Penton, D., Patel, A. & Demolombe, S. in Reviews of Physiology, Biochemistry and Pharmacology Vol. 169 (eds Nilius, B. et al.) 25–41 (Springer International Publishing, 2015).

    Google Scholar 

  11. Parpaite, T. & Coste, B. Piezo channels. Curr. Biol. 27, R250–R252 (2017).

    Article  PubMed  CAS  Google Scholar 

  12. Nourse, J. L. & Pathak, M. M. How cells channel their stress: interplay between Piezo1 and the cytoskeleton. Semin. Cell Dev. Biol. http://dx.doi.org/10.1016/j.semcdb.2017.06.018 (2017). This review summarizes the emerging role of PIEZO1 in internal force sensing.

  13. Li, W., Gao, N. & Yang, M. Current Topics in Membranes (Academic Press, 2016).

    Google Scholar 

  14. Wu, J., Lewis, A. H. & Grandl, J. Touch, tension, and transduction – the function and regulation of Piezo ion channels. Trends Biochem. Sci. 42, 57–71 (2016). This review highlights aspects of Piezo function.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Walsh, C. M., Bautista, D. M. & Lumpkin, E. A. Mammalian touch catches up. Curr. Opin. Neurobiol. 34, 133–139 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  16. Kamajaya, A., Kaiser, J. T., Lee, J., Reid, M. & Rees, D. C. The structure of a conserved Piezo channel domain reveals a topologically distinct β sandwich fold. Structure 22, 1520–1527 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Coste, B. et al. Piezo1 ion channel pore properties are dictated by C-terminal region. Nat. Commun. 6, 7223 (2015).

    Article  PubMed  Google Scholar 

  18. Ge, J. et al. Architecture of the mammalian mechanosensitive Piezo1 channel. Nature 527, 64–69 (2015). This study reports the first medium-resolution cryo-EM structure of PIEZO1.

    Article  PubMed  CAS  Google Scholar 

  19. Prole, D. L. & Taylor, C. W. Identification and analysis of putative homologues of mechanosensitive channels in pathogenic protozoa. PLoS ONE 8, e66068 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Gnanasambandam, R., Bae, C., Gottlieb, P. A. & Sachs, F. Ionic selectivity and permeation properties of human PIEZO1 channels. PLoS ONE 10, e0125503 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Zhao, Q. et al. Ion permeation and mechanotransduction mechanisms of mechanosensitive Piezo channels. Neuron 89, 1248–1263 (2016).

    Article  PubMed  CAS  Google Scholar 

  22. Coste, B. et al. Piezo proteins are pore-forming subunits of mechanically activated channels. Nature 483, 176–181 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Syeda, R. et al. Chemical activation of the mechanotransduction channel Piezo1. eLife 4, e07369 (2015).

    Article  CAS  PubMed Central  Google Scholar 

  24. Lacroix, J. J., Botello-Smith, W. M. & Luo, Y. Chemical gating of the mechanosensitive Piezo1 channel by asymmetric binding of its agonist Yoda1. Preprint at bioRxiv http://dx.doi.org/10.1101/169516 (2017).

  25. Cahalan, S. M. et al. Piezo1 links mechanical forces to red blood cell volume. eLife 4, e07370 (2015).

    Article  CAS  PubMed Central  Google Scholar 

  26. Wang, S. et al. Endothelial cation channel PIEZO1 controls blood pressure by mediating flow-induced ATP release. J. Clin. Invest. 126, 4527–4536 (2016). This study reports a role for PIEZO1 in regulating basal blood pressure in mice.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Bae, C., Sachs, F. & Gottlieb, P. A. The mechanosensitive ion channel Piezo1 is inhibited by the peptide GsMTx4. Biochemistry 50, 6295–6300 (2011).

    Article  PubMed  CAS  Google Scholar 

  28. Alcaino, C., Knutson, K., Gottlieb, P. A., Farrugia, G. & Beyder, A. Mechanosensitive ion channel Piezo2 is inhibited by D-GsMTx4. Channels (Austin) 11, 245–253 (2017).

    Article  Google Scholar 

  29. Pliotas, C. et al. The role of lipids in mechanosensation. Nat. Struct. Mol. Biol. 22, 991–998 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Brohawn, S. G., del Mármol, J. & MacKinnon, R. Crystal structure of the human K2P TRAAK, a lipid- and mechano-sensitive K+ ion channel. Science 335, 436–441 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Árnadóttir, J. & Chalfie, M. Eukaryotic mechanosensitive channels. Annu. Rev. Biophys. 39, 111–137 (2010).

    Article  PubMed  CAS  Google Scholar 

  32. Brohawn, S. G., Campbell, E. B. & MacKinnon, R. Physical mechanism for gating and mechanosensitivity of the human TRAAK K+ channel. Nature 516, 126–130 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Zhang, W. et al. Ankyrin repeats convey force to gate the NOMPC mechanotransduction channel. Cell 162, 1391–1403 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Syeda, R. et al. Piezo1 channels are inherently mechanosensitive. Cell Rep. 17, 1739–1746 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  35. Lewis, A. H. & Grandl, J. Mechanical sensitivity of Piezo1 ion channels can be tuned by cellular membrane tension. eLife 4, e12088 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Cox, C. D. et al. Removal of the mechanoprotective influence of the cytoskeleton reveals PIEZO1 is gated by bilayer tension. Nat. Commun. 7, 10366 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  37. Qi, Y. et al. Membrane stiffening by STOML3 facilitates mechanosensation in sensory neurons. Nat. Commun. 6, 8512 (2015).

    Article  PubMed  CAS  Google Scholar 

  38. Dubin, A. E. et al. Endogenous Piezo1 can confound mechanically activated channel identification and characterization. Neuron 94, 266–270.e3 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Wu, J., Goyal, R. & Grandl, J. Localized force application reveals mechanically sensitive domains of Piezo1. Nat. Commun. 7, 12939 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Davies, P. F. Flow-mediated endothelial mechanotransduction. Physiol. Rev. 75, 519–560 (1995).

    Article  PubMed  CAS  Google Scholar 

  41. Eisenhoffer, G. T. et al. Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia. Nature 484, 546–549 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Poole, K., Herget, R., Lapatsina, L., Ngo, H.-D. & Lewin, G. R. Tuning Piezo ion channels to detect molecular-scale movements relevant for fine touch. Nat. Commun. 5, 3520 (2014).

    Article  PubMed  CAS  Google Scholar 

  43. Lee, W. et al. Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage. Proc. Natl Acad. Sci. USA 111, E5114–E5122 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Lewis, A. H., Cui, A. F., McDonald, M. F. & Grandl, J. Transduction of repetitive mechanical stimuli by Piezo1 and Piezo2 ion channels. Cell Rep. 19, 2572–2585 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Albuisson, J. et al. Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels. Nat. Commun. 4, 1884 (2013).

    Article  PubMed  CAS  Google Scholar 

  46. Andolfo, I. et al. Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1. Blood 121, 3925–3935 (2013).

    Article  PubMed  CAS  Google Scholar 

  47. Bae, C., Gnanasambandam, R., Nicolai, C., Sachs, F. & Gottlieb, P. A. Xerocytosis is caused by mutations that alter the kinetics of the mechanosensitive channel PIEZO1. Proc. Natl Acad. Sci. USA 110, E1162–E1168 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Moroni, M., Servin-Vences, M. R., Fleischer, R. & Lewin, G. R. Voltage-gating of mechanosensitive PIEZO channels. Preprint at bioRxiv http://dx.doi.org/10.1101/156489 (2017).

  49. Schneider, E. R. et al. Neuronal mechanism for acute mechanosensitivity in tactile-foraging waterfowl. Proc. Natl Acad. Sci. USA 111, 14941–14946 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Peyronnet, R. et al. Piezo1-dependent stretch-activated channels are inhibited by Polycystin-2 in renal tubular epithelial cells. EMBO Rep. 14, 1143–1148 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Lapatsina, L., Brand, J., Poole, K., Daumke, O. & Lewin, G. R. Stomatin-domain proteins. Eur. J. Cell Biol. 91, 240–245 (2012).

    Article  PubMed  CAS  Google Scholar 

  52. Retailleau, K. et al. Piezo1 in smooth muscle cells is involved in hypertension-dependent arterial remodeling. Cell Rep. 13, 1161–1171 (2015).

    Article  PubMed  CAS  Google Scholar 

  53. Gottlieb, P. A., Bae, C. & Sachs, F. Gating the mechanical channel Piezo1: a comparison between whole-cell and patch recording. Channels (Austin) 6, 282–289 (2012).

    Article  CAS  Google Scholar 

  54. Jia, Z., Ikeda, R., Ling, J., Viatchenko-Karpinski, V. & Gu, J. G. Regulation of Piezo2 mechanotransduction by static plasma membrane tension in primary afferent neurons. J. Biol. Chem. 291, 9087–9104 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Bae, C., Sachs, F. & Gottlieb, P. A. Protonation of the human PIEZO1 ion channel stabilizes inactivation. J. Biol. Chem. 290, 5167–5173 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Dubin, A. E. et al. Inflammatory signals enhance Piezo2-mediated mechanosensitive currents. Cell Rep. 2, 511–517 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Narayanan, P. et al. Native Piezo2 interactomics identifies Pericentrin as a novel regulator of Piezo2 in somatosensory neurons. J. Proteome Res. 15, 2676–2687 (2016).

    Article  PubMed  CAS  Google Scholar 

  58. Borbiro, I., Badheka, D. & Rohacs, T. Activation of TRPV1 channels inhibits mechanosensitive Piezo channel activity by depleting membrane phosphoinositides. Sci. Signal. 8, ra15 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Bae, C., Gottlieb, P. A. & Sachs, F. Human PIEZO1: removing inactivation. Biophys. J. 105, 880–886 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Hahn, C. & Schwartz, M. A. Mechanotransduction in vascular physiology and atherogenesis. Nat. Rev. Mol. Cell Biol. 10, 53–62 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Li, S., Huang, N. F. & Hsu, S. Mechanotransduction in endothelial cell migration. J. Cell. Biochem. 96, 1110–1126 (2005).

    Article  PubMed  CAS  Google Scholar 

  62. Li, J. et al. Piezo1 integration of vascular architecture with physiological force. Nature 515, 279–282 (2014). This is the first report of a role for PIEZO1 in vascular development.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Ranade, S. S. et al. Piezo1, a mechanically activated ion channel, is required for vascular development in mice. Proc. Natl Acad. Sci. USA 111, 10347–10352 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Zarychanski, R. et al. Mutations in the mechanotransduction protein PIEZO1 are associated with hereditary xerocytosis. Blood 120, 1908–1915 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Faucherre, A., Kissa, K., Nargeot, J., Mangoni, M. E. & Jopling, C. Piezo1plays a role in erythrocyte volume homeostasis. Haematologica 99, 70–75 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Shmukler, B. E. et al. Homozygous knockout of the piezo1 gene in the zebrafish is not associated with anemia. Haematologica 100, e483–e485 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Macara, I. G., Guyer, R., Richardson, G., Huo, Y. & Ahmed, S. M. Epithelial Homeostasis. Curr. Biol. 24, R815–R825 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Eyckmans, J., Boudou, T., Yu, X. & Chen, C. S. A hitchhiker's guide to mechanobiology. Dev. Cell 21, 35–47 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Gudipaty, S. A. et al. Mechanical stretch triggers rapid epithelial cell division through Piezo1. Nature 543, 118–121 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Spier, I. et al. Exome sequencing identifies potential novel candidate genes in patients with unexplained colorectal adenomatous polyposis. Familial Cancer 15, 281–288 (2016).

    Article  PubMed  CAS  Google Scholar 

  71. Pathak, M. M. et al. Stretch-activated ion channel Piezo1 directs lineage choice in human neural stem cells. Proc. Natl Acad. Sci. USA 111, 16148–16153 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Koser, D. E. et al. Mechanosensing is critical for axon growth in the developing brain. Nat. Neurosci. 19, 1592–1598 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Miyamoto, T. et al. Functional role for Piezo1 in stretch-evoked Ca2+ influx and ATP release in urothelial cell cultures. J. Biol. Chem. 289, 16565–16575 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Martins, J. R. et al. Piezo1-dependent regulation of urinary osmolarity. Pflugers Arch. 468, 1197–1206 (2016).

    Article  PubMed  CAS  Google Scholar 

  75. Carr, M. J. & Undem, B. J. Bronchopulmonary afferent nerves. Respirology 8, 291–301 (2003).

    Article  PubMed  Google Scholar 

  76. Kim, S. E., Coste, B., Chadha, A., Cook, B. & Patapoutian, A. The role of Drosophila Piezo in mechanical nociception. Nature 483, 209–212 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Faucherre, A., Nargeot, J., Mangoni, M. E. & Jopling, C. piezo2b regulates vertebrate light touch response. J. Neurosci. 33, 17089–17094 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Ikeda, R. et al. Merkel cells transduce and encode tactile stimuli to drive Aβ-afferent impulses. Cell 157, 664–675 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Maksimovic, S. et al. Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors. Nature 509, 617–621 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Ranade, S. S. et al. Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature 516, 121–125 (2014). This study shows that in mice, PIEZO2 is involved in sensory mechanotransduction.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Woo, S. H. et al. Piezo2 is required for Merkel-cell mechanotransduction. Nature 509, 622–626 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Woo, S. H. et al. Piezo2 is the principal mechanotransduction channel for proprioception. Nat. Neurosci. 18, 1756–1762 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Florez-Paz, D., Bali, K. K., Kuner, R. & Gomis, A. A critical role for Piezo2 channels in the mechanotransduction of mouse proprioceptive neurons. Sci. Rep. 6, 25923 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Chesler, A. T. et al. The role of PIEZO2 in human mechanosensation. N. Engl. J. Med. 375, 1355–1364 (2016). This is the first paper to report that PIEZO2 is essential for mechanosensation in humans.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Mahmud, A. A. et al. Loss of the proprioception and touch sensation channel PIEZO2 in siblings with a progressive form of contractures. Clin. Genet. 91, 470–475 (2016).

    Article  PubMed  CAS  Google Scholar 

  86. Delle Vedove, A. et al. Biallelic loss of proprioception-related PIEZO2 causes muscular atrophy with perinatal respiratory distress, arthrogryposis, and scoliosis. Am. J. Hum. Genet. 99, 1406–1408 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Haliloglu, G. et al. Recessive PIEZO2 stop mutation causes distal arthrogryposis with distal muscle weakness, scoliosis and proprioception defects. J. Hum. Genet. 62, 497–501 (2016).

    Article  PubMed  CAS  Google Scholar 

  88. Nonomura, K. et al. Piezo2 senses airway stretch and mediates lung inflation-induced apnoea. Nature 541, 176–181 (2016). This paper demonstrates an unexpected role for PIEZO2 in respiratory mechanotransduction.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Coste, B. et al. Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of distal arthrogryposis. Proc. Natl Acad. Sci. USA 110, 4667–4672 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Okubo, M. et al. A family of distal arthrogryposis type 5 due to a novel PIEZO2 mutation. Am. J. Med. Genet. A 167, 1100–1106 (2015).

    Article  CAS  Google Scholar 

  91. Tryfon, S., Kontakiotis, T., Mavrofridis, E. & Patakas, D. Hering-breuer reflex in normal adults and in patients with chronic obstructive pulmonary disease and interstitial fibrosis. Respiration 68, 140–144 (2001).

    Article  PubMed  CAS  Google Scholar 

  92. Zhao, B. & Müller, U. The elusive mechanotransduction machinery of hair cells. Curr. Opin. Neurobiol. 34, 172–179 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Wu, Z. et al. Mechanosensory hair cells express two molecularly distinct mechanotransduction channels. Nat. Neurosci. 20, 24–33 (2017).

    Article  PubMed  CAS  Google Scholar 

  94. Mawe, G. M. & Hoffman, J. M. Serotonin signalling in the gut — functions, dysfunctions and therapeutic targets. Nat. Rev. Gastroenterol. Hepatol. 10, 473–486 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  95. Wang, F. et al. Mechanosensitive ion channel Piezo2 is important for enterochromaffin cell response to mechanical forces. J. Physiol. 595, 79–91 (2017).

    Article  PubMed  CAS  Google Scholar 

  96. Tao, B. et al. Piezo2: a candidate biomarker for visceral hypersensitivity in irritable bowel syndrome? J. Neurogastroenterol. Motil. 23, 453–463 (2017).

    Article  Google Scholar 

  97. Rocio Servin-Vences, M., Moroni, M., Lewin, G. R. & Poole, K. Direct measurement of TRPV4 and PIEZO1 activity reveals multiple mechanotransduction pathways in chondrocytes. eLife 6, e21074 (2017).

    Article  PubMed Central  Google Scholar 

  98. Ma, S. et al. Common Piezo1 allele in African populations causes xerocytosis and attenuates Plasmodium infection. Preprint at bioRxiv http://dx.doi.org/10.1101/159830 (2017).

  99. Fotiou, E. et al. Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis. Nat. Commun. 6, 8085 (2015).

    Article  PubMed  Google Scholar 

  100. Lukacs, V. et al. Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia. Nat. Commun. 6, 83829 (2015).

    Article  CAS  Google Scholar 

  101. Chalfie, M. Neurosensory mechanotransduction. Nat. Rev. Mol. Cell Biol. 10, 44–52 (2009).

    Article  PubMed  CAS  Google Scholar 

  102. Maingret, F., Patel, A. J., Lesage, F., Lazdunski, M. & Honoré, E. Mechano- or acid stimulation, two interactive modes of activation of the TREK-1 potassium channel. J. Biol. Chem. 274, 26691–26696 (1999).

    Article  PubMed  CAS  Google Scholar 

  103. Delmas, P. & Coste, B. Mechano-gated ion channels in sensory systems. Cell 155, 278–284 (2013).

    Article  PubMed  CAS  Google Scholar 

  104. Endlich, K., Kliewe, F. & Endlich, N. Stressed podocytes — mechanical forces, sensors, signaling and response. Pflugers Arch. 469, 937–949 (2017).

    Article  PubMed  CAS  Google Scholar 

  105. Ben-Shahar, Y. Sensory functions for degenerin/epithelial sodium channels (DEG/ENaC). Adv. Genet. 76, 1–26 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Hong, G.-S. et al. Tentonin 3/TMEM150c confers distinct mechanosensitive currents in dorsal-root ganglion neurons with proprioceptive function. Neuron 91, 107–118 (2016).

    Article  PubMed  CAS  Google Scholar 

  107. Beyder, A. et al. Mechanosensitivity of Nav1.5, a voltage-sensitive sodium channel. J. Physiol. 588, 4969–4985 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  108. Morris, C. E. & Juranka, P. F. Nav channel mechanosensitivity: activation and inactivation accelerate reversibly with stretch. Biophys. J. 93, 822–833 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Lin, W., Laitko, U., Juranka, P. F. & Morris, C. E. Dual stretch responses of mHCN2 pacemaker channels: accelerated activation, accelerated deactivation. Biophys. J. 92, 1559–1572 (2007).

    Article  PubMed  CAS  Google Scholar 

  110. Calabrese, B., Tabarean, I. V., Juranka, P. & Morris, C. E. Mechanosensitivity of N-type calcium channel currents. Biophys. J. 83, 2560–2574 (2002).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  111. Pathak, M. M. et al. The Hv1 proton channel responds to mechanical stimuli. J. Gen. Physiol. 148, 405–418 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Maneshi, M. M. et al. Mechanical stress activates NMDA receptors in the absence of agonists. Sci. Rep. 7, 39610 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. Ohashi, K., Fujiwara, S. & Mizuno, K. Roles of the cytoskeleton, cell adhesion and rho signalling in mechanosensing and mechanotransduction. J. Biochem. 161, 245–254 (2017).

    PubMed  CAS  Google Scholar 

  114. Glogowska, E. et al. Novel mechanisms of PIEZO1 dysfunction in hereditary xerocytosis. Blood http://dx.doi.org/10.1182/blood-2017-05-786004 (2017).

  115. McMillin, M. J. et al. Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5. Am. J. Hum. Genet. 94, 734–744 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

The authors thank J. Kefauver, K. Marshall and K. Saotome for their helpful comments. A.P. is a Howard Hughes Medical Institute investigator.

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  1. Department of Neuroscience, Howard Hughes Medical Institute, The Scripps Research Institute, La Jolla, 92037, California, USA

    Swetha E. Murthy, Adrienne E. Dubin & Ardem Patapoutian

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A.P., S.E.M. and A.E.D. discussed the content of the article and contributed to the writing and editing of the manuscript. S.E.M. and A.E.D. also contributed by researching data for the article.

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Correspondence to Ardem Patapoutian.

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The authors declare no competing financial interests.

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Glossary

Membrane potential

The voltage across the plasma membrane that is dependent on the charge separated on the outer and inner membrane leaflets; usually, the resting membrane potential is negative (∼−70 to −30 mV depending on the cell type).

Lipid rafts

Membrane subdomains that are ordered assemblies enriched in cholesterol, glycosphingolipids and proteins.

Bradykinin

An inflammatory peptide that activates cognate G protein-coupled receptors.

Dorsal root ganglion (DRG) neurons

Pseudo-unipolar sensory neurons whose cell bodies are located in the dorsal root of the spinal column and extend a single bifurcating axon, one end of which innervates sensory organs and the other which synapses onto neurons in the spinal cord. They are capable of detecting mechanical, chemical and/or thermal stimuli and signal to the central nervous system.

Pericentrin

A multifunctional scaffold for anchoring proteins and protein complexes.

Transient receptor potential cation channel subfamily V member 1

(TRPV1). An ion channel activated by capsaicin and heat that is expressed in a subpopulation of sensory neurons, including nociceptors.

Calpain

A calcium-dependent cytosolic cysteine proteinase with roles in cell migration, differentiation and apoptosis.

Focal adhesions

Contact sites between cells and the extracellular matrix that function as anchor points for the cell and as biochemical signalling centres.

Traction force

A type of force generated within the cell in response to change in its environment. These forces are a result of interactions between actin filaments, adhesion molecules and the extracellular matrix.

Nociceptors

A subpopulation of non-myelinated or lightly myelinated sensory neurons that detect noxious stimuli and are the initial receptors that signal the presence of a stimulus that can cause damage to the organism.

Merkel cells

Specialized epithelial cells present in the skin that are in close contact with the peripheral terminals of low-threshold sensory neurons.

Vagal neurons

Sensory neurons that have their cell bodies within the nodose and jugular ganglia situated in the vagus nerve (tenth cranial nerve) and that innervate internal organs.

Arthrogryposis

A condition characterized by joint contractures causing immobility of the joints, which is generally associated with other disorders.

Enterochromaffin cells

A subset of cells in the epithelium of the lumen of the gastrointestinal tract that regulates secretion of enzymes and bowel movement.

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Murthy, S., Dubin, A. & Patapoutian, A. Piezos thrive under pressure: mechanically activated ion channels in health and disease. Nat Rev Mol Cell Biol 18, 771–783 (2017). https://doi.org/10.1038/nrm.2017.92

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