1932

Abstract

The mechanically activated Piezo channels, including Piezo1 and Piezo2 in mammals, function as key mechanotransducers for converting mechanical force into electrochemical signals. This review highlights key evidence for the potential of Piezo channel drug discovery. First, both mouse and human genetic studies have unequivocally demonstrated the prominent role of Piezo channels in various mammalian physiologies and pathophysiologies, validating their potential as novel therapeutic targets. Second, the cryo-electron microscopy structure of the 2,547-residue mouse Piezo1 trimer has been determined, providing a solid foundation for studying its structure-function relationship and drug action mechanisms and conducting virtual drug screening. Third, Piezo1 chemical activators, named Yoda1 and Jedi1/2, have been identified through high-throughput screening assays, demonstrating the drugability of Piezo channels. However, the pharmacology of Piezo channels is in its infancy. By establishing an integrated drug discovery platform, we may hopefully discover and develop a fleet of Jedi masters for battling Piezo-related human diseases.

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2020-01-06
2024-06-25
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Literature Cited

  1. 1. 
    Ranade SS, Syeda R, Patapoutian A 2015. Mechanically activated ion channels. Neuron 87:1162–79
    [Google Scholar]
  2. 2. 
    Chalfie M. 2009. Neurosensory mechanotransduction. Nat. Rev. Mol. Cell Biol. 10:44–52
    [Google Scholar]
  3. 3. 
    Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S et al. 2010. Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels. Science 330:55–60
    [Google Scholar]
  4. 4. 
    Coste B, Xiao B, Santos JS, Syeda R, Grandl J et al. 2012. Piezo proteins are pore-forming subunits of mechanically activated channels. Nature 483:176–81
    [Google Scholar]
  5. 5. 
    Ge J, Li W, Zhao Q, Li N, Chen M et al. 2015. Architecture of the mammalian mechanosensitive Piezo1 channel. Nature 527:64–69
    [Google Scholar]
  6. 6. 
    Zhao Q, Wu K, Geng J, Chi S, Wang Y et al. 2016. Ion permeation and mechanotransduction mechanisms of mechanosensitive Piezo channels. Neuron 89:1248–63
    [Google Scholar]
  7. 7. 
    Geng J, Zhao Q, Zhang T, Xiao B 2017. In touch with the mechanosensitive Piezo channels: structure, ion permeation, and mechanotransduction. Curr. Top. Membr. 79:159–95
    [Google Scholar]
  8. 8. 
    Gottlieb PA. 2017. A tour de force: the discovery, properties, and function of piezo channels. Curr. Top. Membr. 79:1–36
    [Google Scholar]
  9. 9. 
    Murthy SE, Dubin AE, Patapoutian A 2017. Piezos thrive under pressure: mechanically activated ion channels in health and disease. Nat. Rev. Mol. Cell Biol. 18:771–83
    [Google Scholar]
  10. 10. 
    Wu Z, Grillet N, Zhao B, Cunningham C, Harkins-Perry S et al. 2017. Mechanosensory hair cells express two molecularly distinct mechanotransduction channels. Nat. Neurosci. 20:24–33
    [Google Scholar]
  11. 11. 
    Kim SE, Coste B, Chadha A, Cook B, Patapoutian A 2012. The role of Drosophila Piezo in mechanical nociception. Nature 483:209–12
    [Google Scholar]
  12. 12. 
    Chen X, Wanggou S, Bodalia A, Zhu M, Dong W et al. 2018. A feedforward mechanism mediated by mechanosensitive ion channel PIEZO1 and tissue mechanics promotes glioma aggression. Neuron 100:799–815.e7
    [Google Scholar]
  13. 13. 
    Song Y, Li D, Farrelly O, Miles L, Li F et al. 2019. The mechanosensitive ion channel Piezo inhibits axon regeneration. Neuron 102:373–89.e6
    [Google Scholar]
  14. 14. 
    Faucherre A, Nargeot J, Mangoni ME, Jopling C 2013. piezo2b regulates vertebrate light touch response. J. Neurosci. 33:17089–94
    [Google Scholar]
  15. 15. 
    Schneider ER, Mastrotto M, Laursen WJ, Schulz VP, Goodman JB et al. 2014. Neuronal mechanism for acute mechanosensitivity in tactile-foraging waterfowl. PNAS 111:14941–46
    [Google Scholar]
  16. 16. 
    Honore E, Martins JR, Penton D, Patel A, Demolombe S 2015. The Piezo mechanosensitive ion channels: May the force be with you!. Rev. Physiol. Biochem. Pharmacol. 169:25–41
    [Google Scholar]
  17. 17. 
    Wu J, Lewis AH, Grandl J 2016. Touch, tension, and transduction—the function and regulation of Piezo ion channels. Trends Biochem. Sci. 42:57–71
    [Google Scholar]
  18. 18. 
    Zarychanski R, Schulz VP, Houston BL, Maksimova Y, Houston DS et al. 2012. Mutations in the mechanotransduction protein PIEZO1 are associated with hereditary xerocytosis. Blood 120:1908–15
    [Google Scholar]
  19. 19. 
    Albuisson J, Murthy SE, Bandell M, Coste B, Louis-Dit-Picard H et al. 2013. Dehydrated hereditary stomatocytosis linked to gain-of-function mutations in mechanically activated PIEZO1 ion channels. Nat. Commun. 4:1884
    [Google Scholar]
  20. 20. 
    Alper SL. 2017. Genetic diseases of PIEZO1 and PIEZO2 dysfunction. Curr. Top. Membr. 79:97–134
    [Google Scholar]
  21. 21. 
    Bae C, Gnanasambandam R, Nicolai C, Sachs F, Gottlieb PA 2013. Xerocytosis is caused by mutations that alter the kinetics of the mechanosensitive channel PIEZO1. PNAS 110:E1162–68
    [Google Scholar]
  22. 22. 
    Cinar E, Zhou S, DeCourcey J, Wang Y, Waugh RE, Wan J 2015. Piezo1 regulates mechanotransductive release of ATP from human RBCs. PNAS 112:11783–88
    [Google Scholar]
  23. 23. 
    Cahalan SM, Lukacs V, Ranade SS, Chien S, Bandell M, Patapoutian A 2015. Piezo1 links mechanical forces to red blood cell volume. eLife 4:e07370
    [Google Scholar]
  24. 24. 
    Ma S, Cahalan S, LaMonte G, Grubaugh ND, Zeng W et al. 2018. Common PIEZO1 allele in African populations causes RBC dehydration and attenuates Plasmodium infection. Cell 173:443–55.e12
    [Google Scholar]
  25. 25. 
    Fotiou E, Martin-Almedina S, Simpson MA, Lin S, Gordon K et al. 2015. Novel mutations in PIEZO1 cause an autosomal recessive generalized lymphatic dysplasia with non-immune hydrops fetalis. Nat. Commun. 6:8085
    [Google Scholar]
  26. 26. 
    Lukacs V, Mathur J, Mao R, Bayrak-Toydemir P, Procter M et al. 2015. Impaired PIEZO1 function in patients with a novel autosomal recessive congenital lymphatic dysplasia. Nat. Commun. 6:8329
    [Google Scholar]
  27. 27. 
    Martin-Almedina S, Mansour S, Ostergaard P 2018. Human phenotypes caused by PIEZO1 mutations; one gene, two overlapping phenotypes?. J. Physiol. 596:985–92
    [Google Scholar]
  28. 28. 
    Nonomura K, Lukacs V, Sweet DT, Goddard LM, Kanie A et al. 2018. Mechanically activated ion channel PIEZO1 is required for lymphatic valve formation. PNAS 115:12817–22
    [Google Scholar]
  29. 29. 
    Choi D, Park E, Jung E, Cha B, Lee S et al. 2019. Piezo1 incorporates mechanical force signals into the genetic program that governs lymphatic valve development and maintenance. JCI Insight 4:125068
    [Google Scholar]
  30. 30. 
    Li J, Hou B, Tumova S, Muraki K, Bruns A et al. 2014. Piezo1 integration of vascular architecture with physiological force. Nature 515:7526279–82
    [Google Scholar]
  31. 31. 
    Ranade SS, Qiu Z, Woo SH, Hur SS, Murthy SE et al. 2014. Piezo1, a mechanically activated ion channel, is required for vascular development in mice. PNAS 111:10347–52
    [Google Scholar]
  32. 32. 
    Li J, Hou B, Tumova S, Muraki K, Bruns A et al. 2014. Piezo1 integration of vascular architecture with physiological force. Nature 515:279–82
    [Google Scholar]
  33. 33. 
    Kang H, Hong Z, Zhong M, Klomp J, Bayless KJ et al. 2019. Piezo1 mediates angiogenesis through activation of MT1-MMP signaling. Am. J. Physiol. Cell Physiol. 316:C92–103
    [Google Scholar]
  34. 34. 
    Albarran-Juarez J, Iring A, Wang S, Joseph S, Grimm M et al. 2018. Piezo1 and Gq/G11 promote endothelial inflammation depending on flow pattern and integrin activation. J. Exp. Med. 215:2655–72
    [Google Scholar]
  35. 35. 
    Retailleau K, Duprat F, Arhatte M, Ranade SS, Peyronnet R et al. 2015. Piezo1 in smooth muscle cells is involved in hypertension-dependent arterial remodeling. Cell Rep 13:1161–71
    [Google Scholar]
  36. 36. 
    Wang S, Chennupati R, Kaur H, Iring A, Wettschureck N, Offermanns S 2016. Endothelial cation channel PIEZO1 controls blood pressure by mediating flow-induced ATP release. J. Clin. Investig. 126:124527–36
    [Google Scholar]
  37. 37. 
    Lhomme A, Gilbert G, Pele T, Deweirdt J, Henrion D et al. 2018. Stretch-activated Piezo1 channel in endothelial cells relaxes mouse intrapulmonary arteries. Am. J. Respir. Cell Mol. Biol. 60:6650–58
    [Google Scholar]
  38. 38. 
    Rode B, Shi J, Endesh N, Drinkhill MJ, Webster PJ et al. 2017. Piezo1 channels sense whole body physical activity to reset cardiovascular homeostasis and enhance performance. Nat. Commun. 8:350
    [Google Scholar]
  39. 39. 
    Ranade SS, Woo SH, Dubin AE, Moshourab RA, Wetzel C et al. 2014. Piezo2 is the major transducer of mechanical forces for touch sensation in mice. Nature 516:121–25
    [Google Scholar]
  40. 40. 
    Zhang M, Wang Y, Geng J, Zhou S, Xiao B 2019. Mechanically activated Piezo channels mediate touch and suppress acute mechanical pain response in mice. Cell Rep 26:1419–31.e4
    [Google Scholar]
  41. 41. 
    Woo SH, Ranade S, Weyer AD, Dubin AE, Baba Y et al. 2014. Piezo2 is required for Merkel-cell mechanotransduction. Nature 509:7502622–26
    [Google Scholar]
  42. 42. 
    Murthy SE, Loud MC, Daou I, Marshall KL, Schwaller F et al. 2018. The mechanosensitive ion channel Piezo2 mediates sensitivity to mechanical pain in mice. Sci. Transl. Med. 10:eaat9897
    [Google Scholar]
  43. 43. 
    Ikeda R, Cha M, Ling J, Jia Z, Coyle D, Gu JG 2014. Merkel cells transduce and encode tactile stimuli to drive Aβ-afferent impulses. Cell 157:664–75
    [Google Scholar]
  44. 44. 
    Woo SH, Lukacs V, de Nooij JC, Zaytseva D, Criddle CR et al. 2015. Piezo2 is the principal mechanotransduction channel for proprioception. Nat. Neurosci. 18:1756–62
    [Google Scholar]
  45. 45. 
    Eijkelkamp N, Linley JE, Torres JM, Bee L, Dickenson AH et al. 2013. A role for Piezo2 in EPAC1-dependent mechanical allodynia. Nat. Commun. 4:1682
    [Google Scholar]
  46. 46. 
    Singhmar P, Huo X, Eijkelkamp N, Berciano SR, Baameur F et al. 2016. Critical role for Epac1 in inflammatory pain controlled by GRK2-mediated phosphorylation of Epac1. PNAS 113:113036–41
    [Google Scholar]
  47. 47. 
    Szczot M, Liljencrantz J, Ghitani N, Barik A, Lam R et al. 2018. PIEZO2 mediates injury-induced tactile pain in mice and humans. Sci. Transl. Med. 10:eaat9892
    [Google Scholar]
  48. 48. 
    Feng J, Luo J, Yang P, Du J, Kim BS, Hu H 2018. Piezo2 channel–Merkel cell signaling modulates the conversion of touch to itch. Science 360:530–33
    [Google Scholar]
  49. 49. 
    Chesler AT, Szczot M, Bharucha-Goebel D, Ceko M, Donkervoort S et al. 2016. The role of PIEZO2 in human mechanosensation. N. Engl. J. Med. 375:1355–64
    [Google Scholar]
  50. 50. 
    Delle Vedove A, Storbeck M, Heller R, Holker I, Hebbar M et al. 2016. Biallelic loss of proprioception-related PIEZO2 causes muscular atrophy with perinatal respiratory distress, arthrogryposis, and scoliosis. Am. J. Hum. Genet. 99:1406–8
    [Google Scholar]
  51. 51. 
    Schrenk-Siemens K, Wende H, Prato V, Song K, Rostock C et al. 2015. PIEZO2 is required for mechanotransduction in human stem cell–derived touch receptors. Nat. Neurosci. 18:10–16
    [Google Scholar]
  52. 52. 
    Nonomura K, Woo SH, Chang RB, Gillich A, Qiu Z et al. 2017. Piezo2 senses airway stretch and mediates lung inflation-induced apnoea. Nature 541:176–81
    [Google Scholar]
  53. 53. 
    Coste B, Houge G, Murray MF, Stitziel N, Bandell M et al. 2013. Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of distal arthrogryposis. PNAS 110:4667–72
    [Google Scholar]
  54. 54. 
    McMillin MJ, Beck AE, Chong JX, Shively KM, Buckingham KJ et al. 2014. Mutations in PIEZO2 cause Gordon syndrome, Marden-Walker syndrome, and distal arthrogryposis type 5. Am. J. Hum. Genet. 94:734–44
    [Google Scholar]
  55. 55. 
    Okubo M, Fujita A, Saito Y, Komaki H, Ishiyama A et al. 2015. A family of distal arthrogryposis type 5 due to a novel PIEZO2 mutation. Am. J. Med. Genet. A 167A:1100–6
    [Google Scholar]
  56. 56. 
    Zeng WZ, Marshall KL, Min S, Daou I, Chapleau MW et al. 2018. PIEZOs mediate neuronal sensing of blood pressure and the baroreceptor reflex. Science 362:464–67
    [Google Scholar]
  57. 57. 
    Liao M, Cao E, Julius D, Cheng Y 2013. Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature 504:107–12
    [Google Scholar]
  58. 58. 
    Zhao Q, Zhou H, Chi S, Wang Y, Wang J et al. 2018. Structure and mechanogating mechanism of the Piezo1 channel. Nature 554:487–92
    [Google Scholar]
  59. 59. 
    Guo YR, MacKinnon R. 2017. Structure-based membrane dome mechanism for Piezo mechanosensitivity. eLife 6:e33660
    [Google Scholar]
  60. 60. 
    Saotome K, Murthy SE, Kefauver JM, Whitwam T, Patapoutian A, Ward AB 2018. Structure of the mechanically activated ion channel Piezo1. Nature 554:481–86
    [Google Scholar]
  61. 61. 
    Kamajaya A, Kaiser JT, Lee J, Reid M, Rees DC 2014. The structure of a conserved piezo channel domain reveals a topologically distinct β sandwich fold. Structure 22:1520–27
    [Google Scholar]
  62. 62. 
    Lewis AH, Grandl J. 2015. Mechanical sensitivity of Piezo1 ion channels can be tuned by cellular membrane tension. eLife 4:e12088
    [Google Scholar]
  63. 63. 
    Syeda R, Florendo MN, Cox CD, Kefauver JM, Santos JS et al. 2016. Piezo1 channels are inherently mechanosensitive. Cell Rep 17:1739–46
    [Google Scholar]
  64. 64. 
    Cox CD, Bae C, Ziegler L, Hartley S, Nikolova-Krstevski V et al. 2016. Removal of the mechanoprotective influence of the cytoskeleton reveals PIEZO1 is gated by bilayer tension. Nat. Commun. 7:10366
    [Google Scholar]
  65. 65. 
    Jan YN, Jan LY. 2018. Force-activated ion channels in close-up. Nature 554:469–70
    [Google Scholar]
  66. 66. 
    Gonzales EB, Kawate T, Gouaux E 2009. Pore architecture and ion sites in acid-sensing ion channels and P2X receptors. Nature 460:599–604
    [Google Scholar]
  67. 67. 
    Kawate T, Michel JC, Birdsong WT, Gouaux E 2009. Crystal structure of the ATP-gated P2X4 ion channel in the closed state. Nature 460:592–98
    [Google Scholar]
  68. 68. 
    Zhao Q, Zhou H, Li X, Xiao B 2019. The mechanosensitive Piezo1 channel: a three-bladed propeller-like structure and a lever-like mechanogating mechanism. FEBS J 286:13246170
    [Google Scholar]
  69. 69. 
    Coste B, Murthy SE, Mathur J, Schmidt M, Mechioukhi Y et al. 2015. Piezo1 ion channel pore properties are dictated by C-terminal region. Nat. Commun. 6:7223
    [Google Scholar]
  70. 70. 
    Zhang T, Chi S, Jiang F, Zhao Q, Xiao B 2017. A protein interaction mechanism for suppressing the mechanosensitive Piezo channels. Nat. Commun. 8:1797
    [Google Scholar]
  71. 71. 
    Long SB, Campbell EB, Mackinnon R 2005. Voltage sensor of Kv1.2: structural basis of electromechanical coupling. Science 309:903–8
    [Google Scholar]
  72. 72. 
    Poole K, Herget R, Lapatsina L, Ngo HD, Lewin GR 2014. Tuning Piezo ion channels to detect molecular-scale movements relevant for fine touch. Nat. Commun. 5:3520
    [Google Scholar]
  73. 73. 
    Servin-Vences MR, Moroni M, Lewin GR, Poole K 2017. Direct measurement of TRPV4 and PIEZO1 activity reveals multiple mechanotransduction pathways in chondrocytes. eLife 6:e21074
    [Google Scholar]
  74. 74. 
    Cox CD, Bavi N, Martinac B 2017. Origin of the force: the force-from-lipids principle applied to Piezo channels. Curr. Top. Membr. 79:59–96
    [Google Scholar]
  75. 75. 
    Haselwandter CA, MacKinnon R. 2018. Piezo's membrane footprint and its contribution to mechanosensitivity. eLife 7:e41968
    [Google Scholar]
  76. 76. 
    Wang Y, Chi S, Guo H, Li G, Wang L et al. 2018. A lever-like transduction pathway for long-distance chemical- and mechano-gating of the mechanosensitive Piezo1 channel. Nat. Commun. 9:1300
    [Google Scholar]
  77. 77. 
    Wang Y, Xiao B. 2017. The mechanosensitive Piezo1 channel: structural features and molecular bases underlying its ion permeation and mechanotransduction. J. Physiol. 596:6969–78
    [Google Scholar]
  78. 78. 
    Wu J, Goyal R, Grandl J 2016. Localized force application reveals mechanically sensitive domains of Piezo1. Nat. Commun. 7:12939
    [Google Scholar]
  79. 79. 
    Lewis AH, Cui AF, McDonald MF, Grandl J 2017. Transduction of repetitive mechanical stimuli by Piezo1 and Piezo2 ion channels. Cell Rep 19:2572–85
    [Google Scholar]
  80. 80. 
    Bae C, Gottlieb PA, Sachs F 2013. Human PIEZO1: removing inactivation. Biophys. J. 105:880–86
    [Google Scholar]
  81. 81. 
    Moroni M, Servin-Vences MR, Fleischer R, Sanchez-Carranza O, Lewin GR 2018. Voltage gating of mechanosensitive PIEZO channels. Nat. Commun. 9:1096
    [Google Scholar]
  82. 82. 
    Wu J, Young M, Lewis AH, Martfeld AN, Kalmeta B, Grandl J 2017. Inactivation of mechanically activated Piezo1 ion channels is determined by the C-terminal extracellular domain and the inner pore helix. Cell Rep 21:2357–66
    [Google Scholar]
  83. 83. 
    Zheng W, Gracheva EO, Bagriantsev SN 2019. A hydrophobic gate in the inner pore helix is the major determinant of inactivation in mechanosensitive Piezo channels. eLife 8:e44003
    [Google Scholar]
  84. 84. 
    Borbiro I, Badheka D, Rohacs T 2015. Activation of TRPV1 channels inhibits mechanosensitive Piezo channel activity by depleting membrane phosphoinositides. Sci. Signal. 8:363ra15
    [Google Scholar]
  85. 85. 
    Narayanan P, Hutte M, Kudryasheva G, Taberner FJ, Lechner SG et al. 2018. Myotubularin related protein-2 and its phospholipid substrate PIP2 control Piezo2-mediated mechanotransduction in peripheral sensory neurons. eLife 7:e32346
    [Google Scholar]
  86. 86. 
    Tsuchiya M, Hara Y, Okuda M, Itoh K, Nishioka R et al. 2018. Cell surface flip-flop of phosphatidylserine is critical for PIEZO1-mediated myotube formation. Nat. Commun. 9:2049
    [Google Scholar]
  87. 87. 
    Qi Y, Andolfi L, Frattini F, Mayer F, Lazzarino M, Hu J 2015. Membrane stiffening by STOML3 facilitates mechanosensation in sensory neurons. Nat. Commun. 6:8512
    [Google Scholar]
  88. 88. 
    Romero LO, Massey AE, Mata-Daboin AD, Sierra-Valdez FJ, Chauhan SC et al. 2019. Dietary fatty acids fine-tune Piezo1 mechanical response. Nat. Commun. 10:1200
    [Google Scholar]
  89. 89. 
    Lee W, Leddy HA, Chen Y, Lee SH, Zelenski NA et al. 2014. Synergy between Piezo1 and Piezo2 channels confers high-strain mechanosensitivity to articular cartilage. PNAS 111:E5114–22
    [Google Scholar]
  90. 90. 
    Gottlieb PA, Bae C, Sachs F 2012. Gating the mechanical channel Piezo1: a comparison between whole-cell and patch recording. Channels 6:282–89
    [Google Scholar]
  91. 91. 
    Jia Z, Ikeda R, Ling J, Viatchenko-Karpinski V, Gu JG 2016. Regulation of Piezo2 mechanotransduction by static plasma membrane tension in primary afferent neurons. J. Biol. Chem. 291:9087–104
    [Google Scholar]
  92. 92. 
    Peyronnet R, Martins JR, Duprat F, Demolombe S, Arhatte M et al. 2013. Piezo1-dependent stretch-activated channels are inhibited by Polycystin-2 in renal tubular epithelial cells. EMBO Rep 14:1143–48
    [Google Scholar]
  93. 93. 
    Narayanan P, Sondermann J, Rouwette T, Karaca S, Urlaub H et al. 2016. Native Piezo2 interactomics identifies pericentrin as a novel regulator of Piezo2 in somatosensory neurons. J. Proteome Res. 15:2676–87
    [Google Scholar]
  94. 94. 
    Raouf R, Lolignier S, Sexton JE, Millet Q, Santana-Varela S et al. 2018. Inhibition of somatosensory mechanotransduction by annexin A6. Sci. Signal. 11:eaao2060
    [Google Scholar]
  95. 95. 
    Anderson EO, Schneider ER, Matson JD, Gracheva EO, Bagriantsev SN 2018. TMEM150C/Tentonin3 is a regulator of mechano-gated ion channels. Cell Rep 23:701–8
    [Google Scholar]
  96. 96. 
    Szczot M, Pogorzala LA, Solinski HJ, Young L, Yee P et al. 2017. Cell-type-specific splicing of Piezo2 regulates mechanotransduction. Cell Rep 21:2760–71
    [Google Scholar]
  97. 97. 
    Bae C, Sachs F, Gottlieb PA 2015. Protonation of the human PIEZO1 ion channel stabilizes inactivation. J. Biol. Chem. 290:5167–73
    [Google Scholar]
  98. 98. 
    Dubin AE, Schmidt M, Mathur J, Petrus MJ, Xiao B et al. 2012. Inflammatory signals enhance piezo2-mediated mechanosensitive currents. Cell Rep 2:511–17
    [Google Scholar]
  99. 99. 
    Bae C, Sachs F, Gottlieb PA 2011. The mechanosensitive ion channel Piezo1 is inhibited by the peptide GsMTx4. Biochemistry 50:6295–300
    [Google Scholar]
  100. 100. 
    Clapham DE. 2007. SnapShot: mammalian TRP channels. Cell 129:220
    [Google Scholar]
  101. 101. 
    Suchyna TM. 2017. Piezo channels and GsMTx4: two milestones in our understanding of excitatory mechanosensitive channels and their role in pathology. Progress Biophys. Mol. Biol. 130:244–53
    [Google Scholar]
  102. 102. 
    Gnanasambandam R, Ghatak C, Yasmann A, Nishizawa K, Sachs F et al. 2017. GsMTx4: mechanism of inhibiting mechanosensitive ion channels. Biophys. J. 112:31–45
    [Google Scholar]
  103. 103. 
    Maneshi MM, Ziegler L, Sachs F, Hua SZ, Gottlieb PA 2018. Enantiomeric Aβ peptides inhibit the fluid shear stress response of PIEZO1. Sci. Rep. 8:14267
    [Google Scholar]
  104. 104. 
    Syeda R, Xu J, Dubin AE, Coste B, Mathur J et al. 2015. Chemical activation of the mechanotransduction channel Piezo1. eLife 4:e07369
    [Google Scholar]
  105. 105. 
    Evans EL, Cuthbertson K, Endesh N, Rode B, Blythe NM et al. 2018. Yoda1 analogue (Dooku1) which antagonizes Yoda1-evoked activation of Piezo1 and aortic relaxation. Br. J. Pharmacol. 175:1744–59
    [Google Scholar]
  106. 106. 
    Lacroix JJ, Botello-Smith WM, Luo Y 2018. Probing the gating mechanism of the mechanosensitive channel Piezo1 with the small molecule Yoda1. Nat. Commun. 9:2029
    [Google Scholar]
  107. 107. 
    Shmukler BE, Huston NC, Thon JN, Ni CW, Kourkoulis G et al. 2015. Homozygous knockout of the piezo1 gene in the zebrafish is not associated with anemia. Haematologica 100:e483–85
    [Google Scholar]
  108. 108. 
    Faucherre A, Kissa K, Nargeot J, Mangoni ME, Jopling C 2014. Piezo1 plays a role in erythrocyte volume homeostasis. Haematologica 99:70–5
    [Google Scholar]
  109. 109. 
    Andolfo I, Alper SL, De Franceschi L, Auriemma C, Russo R et al. 2013. Multiple clinical forms of dehydrated hereditary stomatocytosis arise from mutations in PIEZO1. . Blood 121:3925–35
    [Google Scholar]
  110. 110. 
    Glogowska E, Schneider ER, Maksimova Y, Schulz VP, Lezon-Geyda K et al. 2017. Novel mechanisms of PIEZO1 dysfunction in hereditary xerocytosis. Blood 130:1845–56
    [Google Scholar]
  111. 111. 
    Morley LC, Shi J, Gaunt HJ, Hyman AJ, Webster PJ et al. 2018. Piezo1 channels are mechanosensors in human fetoplacental endothelial cells. Mol. Hum. Reprod. 24:510–20
    [Google Scholar]
  112. 112. 
    John L, Ko NL, Gokin A, Gokina N, Mandala M, Osol G 2018. The Piezo1 cation channel mediates uterine artery shear stress mechanotransduction and vasodilation during rat pregnancy. Am. J. Physiol. Heart Circ. Physiol. 315:H1019–26
    [Google Scholar]
  113. 113. 
    Ilkan Z, Wright JR, Goodall AH, Gibbins JM, Jones CI, Mahaut-Smith MP 2017. Evidence for shear-mediated Ca2+ entry through mechanosensitive cation channels in human platelets and a megakaryocytic cell line. J. Biol. Chem. 292:9204–17
    [Google Scholar]
  114. 114. 
    Gudipaty SA, Lindblom J, Loftus PD, Redd MJ, Edes K et al. 2017. Mechanical stretch triggers rapid epithelial cell division through Piezo1. Nature 543:118–21
    [Google Scholar]
  115. 115. 
    Eisenhoffer GT, Loftus PD, Yoshigi M, Otsuna H, Chien CB et al. 2012. Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia. Nature 484:546–49
    [Google Scholar]
  116. 116. 
    Lang K, Breer H, Frick C 2018. Mechanosensitive ion channel Piezo1 is expressed in antral G cells of murine stomach. Cell Tissue Res 371:251–60
    [Google Scholar]
  117. 117. 
    Romac JM, Shahid RA, Swain SM, Vigna SR, Liddle RA 2018. Piezo1 is a mechanically activated ion channel and mediates pressure induced pancreatitis. Nat. Commun. 9:1715
    [Google Scholar]
  118. 118. 
    Martins JR, Penton D, Peyronnet R, Arhatte M, Moro C et al. 2016. Piezo1-dependent regulation of urinary osmolarity. Pflugers Arch 468:1197–206
    [Google Scholar]
  119. 119. 
    Miyamoto T, Mochizuki T, Nakagomi H, Kira S, Watanabe M et al. 2014. Functional role for Piezo1 in stretch-evoked Ca2+ influx and ATP release in urothelial cell cultures. J. Biol. Chem. 289:2316565–75
    [Google Scholar]
  120. 120. 
    Ihara T, Mitsui T, Nakamura Y, Kanda M, Tsuchiya S et al. 2018. The oscillation of intracellular Ca2+ influx associated with the circadian expression of Piezo1 and TRPV4 in the bladder urothelium. Sci. Rep. 8:5699
    [Google Scholar]
  121. 121. 
    Liu Q, Sun B, Zhao J, Wang Q, An F et al. 2018. Increased Piezo1 channel activity in interstitial Cajal-like cells induces bladder hyperactivity by functionally interacting with NCX1 in rats with cyclophosphamide-induced cystitis. Exp. Mol. Med. 50:60
    [Google Scholar]
  122. 122. 
    Koser DE, Thompson AJ, Foster SK, Dwivedy A, Pillai EK et al. 2016. Mechanosensing is critical for axon growth in the developing brain. Nat. Neurosci. 19:1592–98
    [Google Scholar]
  123. 123. 
    Dong TX, Othy S, Jairaman A, Skupsky J, Zavala A et al. 2017. T-cell calcium dynamics visualized in a ratiometric tdTomato-GCaMP6f transgenic reporter mouse. eLife 6:e32417
    [Google Scholar]
  124. 124. 
    Liu CSC, Raychaudhuri D, Paul B, Chakrabarty Y, Ghosh AR et al. 2018. Cutting edge: Piezo1 mechanosensors optimize human T cell activation. J. Immunol. 200:1255–60
    [Google Scholar]
  125. 125. 
    Hennes A, Held K, Boretto M, De Clercq K, Van den Eynde C et al. 2019. Functional expression of the mechanosensitive PIEZO1 channel in primary endometrial epithelial cells and endometrial organoids. Sci. Rep. 9:1779
    [Google Scholar]
  126. 126. 
    Sugimoto A, Miyazaki A, Kawarabayashi K, Shono M, Akazawa Y et al. 2017. Piezo type mechanosensitive ion channel component 1 functions as a regulator of the cell fate determination of mesenchymal stem cells. Sci. Rep. 7:17696
    [Google Scholar]
  127. 127. 
    Pathak MM, Nourse JL, Tran T, Hwe J, Arulmoli J et al. 2014. Stretch-activated ion channel Piezo1 directs lineage choice in human neural stem cells. PNAS 111:16148–53
    [Google Scholar]
  128. 128. 
    Gao Q, Cooper PR, Walmsley AD, Scheven BA 2017. Role of Piezo channels in ultrasound-stimulated dental stem cells. J. Endod. 43:1130–36
    [Google Scholar]
  129. 129. 
    Del Marmol JI, Touhara KK, Croft G, MacKinnon R 2018. Piezo1 forms a slowly-inactivating mechanosensory channel in mouse embryonic stem cells. eLife 7:e33149
    [Google Scholar]
  130. 130. 
    He L, Si G, Huang J, Samuel ADT, Perrimon N 2018. Mechanical regulation of stem-cell differentiation by the stretch-activated Piezo channel. Nature 555:103–6
    [Google Scholar]
  131. 131. 
    McHugh BJ, Murdoch A, Haslett C, Sethi T 2012. Loss of the integrin-activating transmembrane protein Fam38A (Piezo1) promotes a switch to a reduced integrin-dependent mode of cell migration. PLOS ONE 7:e40346
    [Google Scholar]
  132. 132. 
    Spier I, Kerick M, Drichel D, Horpaopan S, Altmuller J et al. 2016. Exome sequencing identifies potential novel candidate genes in patients with unexplained colorectal adenomatous polyposis. Fam. Cancer 15:281–88
    [Google Scholar]
  133. 133. 
    Li C, Rezania S, Kammerer S, Sokolowski A, Devaney T et al. 2015. Piezo1 forms mechanosensitive ion channels in the human MCF-7 breast cancer cell line. Sci. Rep. 5:8364
    [Google Scholar]
  134. 134. 
    Maksimovic S, Nakatani M, Baba Y, Nelson AM, Marshall KL et al. 2014. Epidermal Merkel cells are mechanosensory cells that tune mammalian touch receptors. Nature 509:617–21
    [Google Scholar]
  135. 135. 
    Florez-Paz D, Bali KK, Kuner R, Gomis A 2016. A critical role for Piezo2 channels in the mechanotransduction of mouse proprioceptive neurons. Sci. Rep. 6:25923
    [Google Scholar]
  136. 136. 
    Hu Y, Wang Z, Liu T, Zhang W 2019. Piezo-like gene regulates locomotion in Drosophila larvae. Cell Rep 26:1369–77.e4
    [Google Scholar]
  137. 137. 
    Alcaino C, Knutson KR, Treichel AJ, Yildiz G, Strege PR et al. 2018. A population of gut epithelial enterochromaffin cells is mechanosensitive and requires Piezo2 to convert force into serotonin release. PNAS 115:E7632–41
    [Google Scholar]
  138. 138. 
    Wang F, Knutson K, Alcaino C, Linden DR, Gibbons SJ et al. 2017. Mechanosensitive ion channel Piezo2 is important for enterochromaffin cell response to mechanical forces. J. Physiol. 595:79–91
    [Google Scholar]
  139. 139. 
    Pardo-Pastor C, Rubio-Moscardo F, Vogel-Gonzalez M, Serra SA, Afthinos A et al. 2018. Piezo2 channel regulates RhoA and actin cytoskeleton to promote cell mechanobiological responses. PNAS 115:1925–30
    [Google Scholar]
  140. 140. 
    Zhao Q, Zhou H, Chi S, Wang Y, Wang J et al. 2018. Structure and mechanogating mechanism of the Piezo1 channel. Nature 554:7693487–92
    [Google Scholar]
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