1932

Abstract

Transient receptor potential (TRP) ion channels are sophisticated signaling machines that detect a wide variety of environmental and physiological signals. Every cell in the body expresses one or more members of the extended TRP channel family, which consists of over 30 subtypes, each likely possessing distinct pharmacological, biophysical, and/or structural attributes. While the function of some TRP subtypes remains enigmatic, those involved in sensory signaling are perhaps best characterized and have served as models for understanding how these excitatory ion channels serve as polymodal signal integrators. With the recent resolution revolution in cryo–electron microscopy, these and other TRP channel subtypes are now yielding their secrets to detailed atomic analysis, which is beginning to reveal structural underpinnings of stimulus detection and gating, ion permeation, and allosteric mechanisms governing signal integration. These insights are providing a framework for designing and evaluating modality-specific pharmacological agents for treating sensory and other TRP channel–associated disorders.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-biochem-032620-105738
2022-06-21
2024-10-13
Loading full text...

Full text loading...

/deliver/fulltext/biochem/91/1/annurev-biochem-032620-105738.html?itemId=/content/journals/10.1146/annurev-biochem-032620-105738&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Cosens DJ, Manning A. 1969. Abnormal electroretinogram from a Drosophila mutant. Nature 224:285–87
    [Google Scholar]
  2. 2.
    Hardie RC, Minke B. 1992. The trp gene is essential for a light-activated Ca2+ channel in Drosophila photoreceptors. Neuron 8:643–51
    [Google Scholar]
  3. 3.
    Montell C, Jones K, Hafen E, Rubin G. 1985. Rescue of the Drosophila phototransduction mutation trp by germline transformation. Science 230:1040–43
    [Google Scholar]
  4. 4.
    Montell C, Rubin GM. 1989. Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron 2:1313–23
    [Google Scholar]
  5. 5.
    Hardie RC. 2001. Phototransduction in Drosophila melanogaster. J. Exp. Biol. 204:3403–9
    [Google Scholar]
  6. 6.
    Smith DP, Stamnes MA, Zucker CS. 1991. Signal transduction in the visual system of Drosophila. Annu. Rev. Cell Biol. 7:161–90
    [Google Scholar]
  7. 7.
    Julius D 2013. TRP channels and pain. Annu. Rev. Cell Dev. Biol. 29:355–84
    [Google Scholar]
  8. 8.
    Clapham DE. 2003. TRP channels as cellular sensors. Nature 426:517–24
    [Google Scholar]
  9. 9.
    Ramsey IS, Delling M, Clapham DE. 2006. An introduction to TRP channels. Annu. Rev. Physiol. 68:619–47
    [Google Scholar]
  10. 10.
    Nilius B, Owsianik G. 2011. The transient receptor potential family of ion channels. Genome Biol. 12:218
    [Google Scholar]
  11. 11.
    Venkatachalam K, Montell C. 2007. TRP Channels.. Annu. Rev. Biochem. 76:387–417
    [Google Scholar]
  12. 12.
    Vay L, Gu C, McNaughton PA. 2012. The thermo-TRP ion channel family: properties and therapeutic implications. Br. J. Pharmacol. 165:787–801
    [Google Scholar]
  13. 13.
    Mochizuki T, Wu G, Hayashi T, Xenophontos SL, Veldhuisen B et al. 1996. PKD2, a gene for polycystic kidney disease that encodes an integral membrane protein. Science 272:1339–42
    [Google Scholar]
  14. 14.
    Nilius B, Owsianik G, Voets T, Peters JA. 2007. Transient receptor potential cation channels in disease. Physiol. Rev. 87:165–217
    [Google Scholar]
  15. 15.
    Nilius B, Voets T. 2013. The puzzle of TRPV4 channelopathies. EMBO Rep 14:152–63
    [Google Scholar]
  16. 16.
    Kremeyer B, Lopera F, Cox JJ, Momin A, Rugiero F et al. 2010. A gain-of-function mutation in TRPA1 causes familial episodic pain syndrome. Neuron 66:671–80
    [Google Scholar]
  17. 17.
    Sexton JE, Vernon J, Wood JN 2014. TRPs and pain. Mammalian Transient Receptor Potential (TRP) Cation Channels: Volume II B Nilius, V Flockerzi 873–97 Cham, Switz: Springer Int. Publ.
    [Google Scholar]
  18. 18.
    McKemy DD, Neuhausser WM, Julius D 2002. Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature 416:52–58
    [Google Scholar]
  19. 19.
    Jordt S-E, Bautista DM, Chuang H-H, McKemy DD, Zygmunt PM et al. 2004. Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature 427:260–65
    [Google Scholar]
  20. 20.
    Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D 1997. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature 389:816–24
    [Google Scholar]
  21. 21.
    Peier AM, Moqrich A, Hergarden AC, Reeve AJ, Andersson DA et al. 2002. A TRP channel that senses cold stimuli and menthol. Cell 108:705–15
    [Google Scholar]
  22. 22.
    Bandell M, Story GM, Hwang SW, Viswanath V, Eid SR et al. 2004. Noxious cold ion channel TRPA1 is activated by pungent compounds and bradykinin. Neuron 41:849–57
    [Google Scholar]
  23. 23.
    Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H et al. 1998. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron 21:531–43
    [Google Scholar]
  24. 24.
    Laing RJ, Dhaka A. 2016. ThermoTRPs and pain. Neuroscientist 22:171–87
    [Google Scholar]
  25. 25.
    Montell C. 2005. The TRP superfamily of cation channels. Sci. STKE 2005:re3
    [Google Scholar]
  26. 26.
    Zhao Y, McVeigh BM, Moiseenkova-Bell VY. 2021. Structural pharmacology of TRP channels. J. Mol. Biol. 433:166914
    [Google Scholar]
  27. 27.
    Long SB, Campbell EB, MacKinnon R. 2005. Crystal structure of a mammalian voltage-dependent Shaker family K+ channel. Science 309:897–903
    [Google Scholar]
  28. 28.
    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]
  29. 29.
    Cao E. 2020. Structural mechanisms of transient receptor potential ion channels. J. Gen. Physiol. 152:e201811998
    [Google Scholar]
  30. 30.
    Madej MG, Ziegler CM. 2018. Dawning of a new era in TRP channel structural biology by cryo-electron microscopy. Pflügers Arch. 470:213–25
    [Google Scholar]
  31. 31.
    Herzig V, Cristofori-Armstrong B, Israel MR, Nixon SA, Vetter I, King GF. 2020. Animal toxins—Nature's evolutionary-refined toolkit for basic research and drug discovery. Biochem. Pharmacol. 181:114096
    [Google Scholar]
  32. 32.
    Vetter I, Lewis RJ. 2011. Natural product ligands of TRP channels. Transient Receptor Potential Channels MS Islam 41–85 Dordrecht, Neth: Springer
    [Google Scholar]
  33. 33.
    Geppetti P, Nassini R, Materazzi S, Benemei S. 2008. The concept of neurogenic inflammation. Br. J. Urol. Int. 101:2–6
    [Google Scholar]
  34. 34.
    Liu B, Qin F. 2005. Functional control of cold- and menthol-sensitive TRPM8 ion channels by phosphatidylinositol 4,5-bisphosphate. J. Neurosci. 25:1674–81
    [Google Scholar]
  35. 35.
    Chuang H-H, Neuhausser WM, Julius D 2004. The super-cooling agent icilin reveals a mechanism of coincidence detection by a temperature-sensitive TRP channel. Neuron 43:859–69
    [Google Scholar]
  36. 36.
    Rohacs T, Lopes CMB, Michailidis I, Logothetis DE. 2005. PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain. Nat. Neurosci. 8:626–34
    [Google Scholar]
  37. 37.
    Bautista DM, Jordt S-E, Nikai T, Tsuruda PR, Read AJ et al. 2006. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell 124:1269–82
    [Google Scholar]
  38. 38.
    Bautista DM, Pellegrino M, Tsunozaki M. 2013. TRPA1: a gatekeeper for inflammation. Annu. Rev. Physiol. 75:181–200
    [Google Scholar]
  39. 39.
    Xing H, Chen M, Ling J, Tan W, Gu JG. 2007. TRPM8 mechanism of cold allodynia after chronic nerve injury. J. Neurosci. 27:13680–90
    [Google Scholar]
  40. 40.
    Descoeur J, Pereira V, Pizzoccaro A, Francois A, Ling B et al. 2011. Oxaliplatin-induced cold hypersensitivity is due to remodelling of ion channel expression in nociceptors. EMBO Mol. Med. 3:266–78
    [Google Scholar]
  41. 41.
    Souza Monteiro de Araujo D, Nassini R, Geppetti P, Logu FD. 2020. TRPA1 as a therapeutic target for nociceptive pain. Expert Opin. Ther. Targets 24:997–1008
    [Google Scholar]
  42. 42.
    Gunthorpe MJ, Chizh BA. 2009. Clinical development of TRPV1 antagonists: targeting a pivotal point in the pain pathway. Drug Discov. Today 14:56–67
    [Google Scholar]
  43. 43.
    Moran MM, Szallasi A. 2018. Targeting nociceptive transient receptor potential channels to treat chronic pain: current state of the field. Br. J. Pharmacol. 175:2185–203
    [Google Scholar]
  44. 44.
    Jord S-E, Tominaga M, Julius D 2000. Acid potentiation of the capsaicin receptor determined by a key extracellular site. PNAS 97:8134–39
    [Google Scholar]
  45. 45.
    Cao E, Liao M, Cheng Y, Julius D 2013. TRPV1 structures in distinct conformations reveal activation mechanisms. Nature 504:113–18
    [Google Scholar]
  46. 46.
    Zhang K, Julius D, Cheng Y 2021. Structural snapshots of TRPV1 reveal mechanism of polymodal functionality. Cell 184:5138–50
    [Google Scholar]
  47. 47.
    Geron M, Hazan A, Priel A. 2017. Animal toxins providing insights into TRPV1 activation mechanism. Toxins 9:326
    [Google Scholar]
  48. 48.
    Swartz KJ, MacKinnon R. 1997. Mapping the receptor site for hanatoxin, a gating modifier of voltage-dependent K+ channels. Neuron 18:675–82
    [Google Scholar]
  49. 49.
    Swartz KJ. 2007. Tarantula toxins interacting with voltage sensors in potassium channels. Toxicon 49:213–30
    [Google Scholar]
  50. 50.
    Bohlen CJ, Priel A, Zhou S, King D, Siemens J, Julius D 2010. A bivalent tarantula toxin activates the capsaicin receptor, TRPV1, by targeting the outer pore domain. Cell 141:834–45
    [Google Scholar]
  51. 51.
    Siemens J, Zhou S, Piskorowski R, Nikai T, Lumpkin EA et al. 2006. Spider toxins activate the capsaicin receptor to produce inflammatory pain. Nature 444:208–12
    [Google Scholar]
  52. 52.
    Bohlen CJ, Julius D 2012. Receptor-targeting mechanisms of pain-causing toxins: How ow?. Toxicon 60:254–64
    [Google Scholar]
  53. 53.
    Gao Y, Cao E, Julius D, Cheng Y 2016. TRPV1 structures in nanodiscs reveal mechanisms of ligand and lipid action. Nature 534:347–51
    [Google Scholar]
  54. 54.
    Bae C, Swartz KJ 2016. Structural insights into the mechanism of activation of the TRPV1 channel by a membrane-bound tarantula toxin. eLife 5:e11273
    [Google Scholar]
  55. 55.
    Hughes TET, Lodowski DT, Huynh KW, Yazici A, Rosario JD et al. 2018. Structural basis of TRPV5 channel inhibition by econazole revealed by cryo-EM. Nat. Struct. Mol. Biol. 25:53–60
    [Google Scholar]
  56. 56.
    Wang Q, Corey R, Hedger G, Aryal P, Grieben M et al. 2019. Lipid interactions of a ciliary membrane TRP channel: simulation and structural studies of polycystin-2. Structure 28:169–84.e5
    [Google Scholar]
  57. 57.
    Zubcevic L, Hsu AL, Borgnia MJ, Lee S-Y 2019. Symmetry transitions during gating of the TRPV2 ion channel in lipid membranes. eLife 8:e45779
    [Google Scholar]
  58. 58.
    Liu C, Reese R, Vu S, Rougé L, Shields SD et al. 2020. A non-covalent ligand reveals biased agonism of the TRPA1 ion channel. Neuron 109:273–84.e4
    [Google Scholar]
  59. 59.
    Suo Y, Wang Z, Zubcevic L, Hsu AL, He Q et al. 2020. Structural insights into electrophile irritant sensing by the human TRPA1 channel. Neuron 105:882–94
    [Google Scholar]
  60. 60.
    Diver MM, Cheng Y, Julius D 2019. Structural insights into TRPM8 inhibition and desensitization. Science 365:1434–40
    [Google Scholar]
  61. 61.
    Yin Y, Le SC, Hsu AL, Borgnia MJ, Yang H, Lee SY 2019. Structural basis of cooling agent and lipid sensing by the cold-activated TRPM8 channel. Science 363:eaav9334
    [Google Scholar]
  62. 62.
    Hinman A, Chuang H-H, Bautista DM, Julius D 2006. TRP channel activation by reversible covalent modification. PNAS 103:19564–68
    [Google Scholar]
  63. 63.
    Macpherson LJ, Dubin AE, Evans MJ, Marr F, Schultz PG et al. 2007. Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines. Nature 445:541–45
    [Google Scholar]
  64. 64.
    Paulsen CE, Armache JP, Gao Y, Cheng Y, Julius D 2015. Structure of the TRPA1 ion channel suggests regulatory mechanisms. Nature 520:511–17
    [Google Scholar]
  65. 65.
    Zhao J, Lin King JV, Paulsen CE, Cheng Y, Julius D 2020. Irritant-evoked activation and calcium modulation of the TRPA1 receptor. Nature 585:141–45
    [Google Scholar]
  66. 66.
    Parks TA, Bahia PK, Taylor-Clark TE. 2021. Functional evidence of distinct electrophile-induced activation states of the ion channel TRPA1. Biochem. Biophys. Rep. 27:101044
    [Google Scholar]
  67. 67.
    Bahia PK, Parks TA, Stanford KR, Mitchell DA, Varma S et al. 2016. The exceptionally high reactivity of Cys 621 is critical for electrophilic activation of the sensory nerve ion channel TRPA1. J. Gen. Physiol. 147:451–65
    [Google Scholar]
  68. 68.
    Lin King JV, Emrick JJ, Kelly MJS, Herzig V, King GF et al. 2019. A cell-penetrating scorpion toxin enables mode-specific modulation of TRPA1 and pain. Cell 178:1362–74
    [Google Scholar]
  69. 69.
    Su Q, Hu F, Ge X, Lei J, Yu S et al. 2018. Structure of the human PKD1-PKD2 complex. Science 361:eaat9819
    [Google Scholar]
  70. 70.
    Dang S, van Goor MK, Asarnow D, Wang Y, Julius D et al. 2019. Structural insight into TRPV5 channel function and modulation. PNAS 116:8869–78
    [Google Scholar]
  71. 71.
    Hughes TET, Pumroy RA, Yazici AT, Kasimova MA, Fluck EC et al. 2018. Structural insights on TRPV5 gating by endogenous modulators. Nat. Commun. 9:4198
    [Google Scholar]
  72. 72.
    Singh AK, McGoldrick LL, Sobolevsky AI. 2018. Structure and gating mechanism of the transient receptor potential channel TRPV3. Nat. Struct. Mol. Biol. 25:805–13
    [Google Scholar]
  73. 73.
    Deng Z, Paknejad N, Maksaev G, Sala-Rabanal M, Nichols CG et al. 2018. Cryo-EM and X-ray structures of TRPV4 reveal insight into ion permeation and gating mechanisms. Nat. Struct. Mol. Biol. 25:252–60
    [Google Scholar]
  74. 74.
    Gracheva EO, Ingolia NT, Kelly YM, Cordero-Morales JF, Hollopeter G et al. 2010. Molecular basis of infrared detection by snakes. Nature 464:1006–11
    [Google Scholar]
  75. 75.
    Cordero-Morales JF, Gracheva EO, Julius D 2011. Cytoplasmic ankyrin repeats of transient receptor potential A1 (TRPA1) dictate sensitivity to thermal and chemical stimuli. PNAS 108:E1184–91
    [Google Scholar]
  76. 76.
    Yin Y, Wu M, Zubcevic L, Borschel WF, Lander GC, Lee S-Y. 2018. Structure of the cold- and menthol-sensing ion channel TRPM8. Science 359:237–41
    [Google Scholar]
  77. 77.
    Tang Q, Guo W, Zheng L, Wu J-X, Liu M et al. 2018. Structure of the receptor-activated human TRPC6 and TRPC3 ion channels. Cell Res. 28:746–55
    [Google Scholar]
  78. 78.
    Kim D, Cavanaugh EJ. 2007. Requirement of a soluble intracellular factor for activation of transient receptor potential A1 by pungent chemicals: role of inorganic polyphosphates. J. Neurosci. 27:6500–9
    [Google Scholar]
  79. 79.
    Wang YY, Chang RB, Waters HN, McKemy DD, Liman ER. 2008. The nociceptor ion channel TRPA1 is potentiated and inactivated by permeating calcium ions. J. Biol. Chem. 283:32691–703
    [Google Scholar]
  80. 80.
    Chung M-K, Güler AD, Caterina MJ. 2008. TRPV1 shows dynamic ionic selectivity during agonist stimulation. Nat. Neurosci. 11:555–64
    [Google Scholar]
  81. 81.
    Chen J, Kim D, Bianchi BR, Cavanaugh EJ, Faltynek CR et al. 2009. Pore dilation occurs in TRPA1 but not in TRPM8 channels. Mol. Pain 5:3
    [Google Scholar]
  82. 82.
    McCoy DD, Palkar R, Yang Y, Ongun S, McKemy DD. 2017. Cellular permeation of large molecules mediated by TRPM8 channels. Neurosci. Lett. 639:59–67
    [Google Scholar]
  83. 83.
    Binshtok AM, Bean BP, Woolf CJ. 2007. Inhibition of nociceptors by TRPV1-mediated entry of impermeant sodium channel blockers. Nature 449:607–10
    [Google Scholar]
  84. 84.
    Puopolo M, Binshtok AM, Yao G-L, Oh SB, Woolf CJ, Bean BP. 2013. Permeation and block of TRPV1 channels by the cationic lidocaine derivative QX-314. J. Neurophysiol. 109:1704–12
    [Google Scholar]
  85. 85.
    McGoldrick LL, Singh AK, Saotome K, Yelshanskaya MV, Twomey EC et al. 2017. Opening of the human epithelial calcium channel TRPV6. Nature 553:233–37
    [Google Scholar]
  86. 86.
    Jara-Oseguera A, Huffer KE, Swartz KJ 2019. The ion selectivity filter is not an activation gate in TRPV1–3 channels. eLife 8:e51212
    [Google Scholar]
  87. 87.
    Myers BR, Bohlen CJ, Julius D 2008. A yeast genetic screen reveals a critical role for the pore helix domain in TRP channel gating. Neuron 58:362–73
    [Google Scholar]
  88. 88.
    Balestrini A, Joseph V, Dourado M, Reese RM, Shields SD et al. 2021. A TRPA1 inhibitor suppresses neurogenic inflammation and airway contraction for asthma treatment. J. Exp. Med. 218:e20201637
    [Google Scholar]
  89. 89.
    Chung MK, Guler AD, Caterina MJ. 2008. TRPV1 shows dynamic ionic selectivity during agonist stimulation. Nat. Neurosci. 11:555–64
    [Google Scholar]
  90. 90.
    Bean BP. 2015. Pore dilation reconsidered. Nat. Neurosci. 18:1534–35
    [Google Scholar]
  91. 91.
    Terrett JA, Chen H, Shore DG, Villemure E, Larouche-Gauthier R et al. 2021. Tetrahydrofuran-based transient receptor potential ankyrin 1 (TRPA1) antagonists: ligand-based discovery, activity in a rodent asthma model, and mechanism-of-action via cryogenic electron microscopy. J. Med. Chem. 64:3843–69
    [Google Scholar]
  92. 92.
    Zubcevic L, Lee S-Y. 2019. The role of π-helices in TRP channel gating. Curr. Opin. Struct. Biol. 58:314–23
    [Google Scholar]
  93. 93.
    Matos-Cruz V, Schneider ER, Mastrotto M, Merriman DK, Bagriantsev SN, Gracheva EO. 2017. Molecular prerequisites for diminished cold sensitivity in ground squirrels and hamsters. Cell Rep 21:3329–37
    [Google Scholar]
  94. 94.
    Zhang F, Jara-Oseguera A, Chang T-H, Bae C, Hanson SM, Swartz KJ. 2018. Heat activation is intrinsic to the pore domain of TRPV1. PNAS 115:E317–24
    [Google Scholar]
  95. 95.
    Brauchi S, Orta G, Salazar M, Rosenmann E, Latorre R. 2006. A hot-sensing cold receptor: C-terminal domain determines thermosensation in transient receptor potential channels. J. Neurosci. 26:4835–40
    [Google Scholar]
  96. 96.
    Clapham DE, Miller C. 2011. A thermodynamic framework for understanding temperature sensing by transient receptor potential (TRP) channels. PNAS 108:19492–97
    [Google Scholar]
  97. 97.
    Nadezhdin KD, Neuberger A, Trofimov YA, Krylov NA, Sinica V et al. 2021. Structural mechanism of heat-induced opening of a temperature-sensitive TRP channel. Nat. Struct. Mol. Biol. 28:564–72
    [Google Scholar]
  98. 98.
    Kwon DH, Zhang F, Suo Y, Bouvette J, Borgnia MJ, Lee S-Y. 2021. Heat-dependent opening of TRPV1 in the presence of capsaicin. Nat. Struct. Mol. Biol. 28:554–63
    [Google Scholar]
  99. 99.
    Tao X, Lee A, Limapichat W, Dougherty DA, MacKinnon R. 2010. A gating charge transfer center in voltage sensors. Science 328:67–73
    [Google Scholar]
  100. 100.
    Nilius B, Talavera K, Owsianik G, Prenen J, Droogmans G, Voets T. 2005. Gating of TRP channels: a voltage connection?. J. Physiol. 567:35–44
    [Google Scholar]
  101. 101.
    Hardie RC. 2007. TRP channels and lipids: from Drosophila to mammalian physiology. J. Physiol. 578:9–24
    [Google Scholar]
  102. 102.
    Autzen HE, Myasnikov AG, Campbell MG, Asarnow D, Julius D, Cheng Y 2018. Structure of the human TRPM4 ion channel in a lipid nanodisc. Science 359:228–32
    [Google Scholar]
  103. 103.
    Duan J, Li J, Bo Z, Chen G-L, Peng X et al. 2018. Structure of the mouse TRPC4 ion channel. Nat. Commun. 9:3102
    [Google Scholar]
  104. 104.
    Ruan Z, Haley E, Orozco IJ, Sabat M, Myers R et al. 2021. Structures of the TRPM5 channel elucidate mechanisms of activation and inhibition. Nat. Struct. Mol. Biol. 28:604–13
    [Google Scholar]
  105. 105.
    Suh B-C, Hille B. 2008. PIP2 is a necessary cofactor for ion channel function: How and why?. Annu. Rev. Biophys. 37:175–95
    [Google Scholar]
  106. 106.
    Rohacs T 2014. Phosphoinositide regulation of TRP channels. Mammalian Transient Receptor Potential (TRP) Cation Channels: Volume II B Nilius, V Flockerzi 1143–76 Cham, Switz: Springer Int. Publ.
    [Google Scholar]
  107. 107.
    Qin F 2007. Regulation of TRP ion channels by phosphatidylinositol-4,5-bisphosphate. Transient Receptor Potential (TRP) Channels V Flockerzi, B Nilius 509–25 Berlin: Springer
    [Google Scholar]
  108. 108.
    Zheng W, Cai R, Hofmann L, Nesin V, Hu Q et al. 2018. Direct binding between Pre-S1 and TRP-like domains in TRPP channels mediates gating and functional regulation by PIP2. Cell Rep 22:1560–73
    [Google Scholar]
  109. 109.
    Harraz OF, Longden TA, Hill-Eubanks D, Nelson MT 2018. PIP2 depletion promotes TRPV4 channel activity in mouse brain capillary endothelial cells. eLife 7:e38689
    [Google Scholar]
  110. 110.
    Chuang H-h, Prescott ED, Kong H, Shields S, Jordt S-E et al. 2001. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature 411:957–62
    [Google Scholar]
  111. 111.
    Prescott ED, Julius D 2003. A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity. Science 300:1284–88
    [Google Scholar]
  112. 112.
    Zhang X, Huang J, McNaughton PA. 2005. NGF rapidly increases membrane expression of TRPV1 heat-gated ion channels. EMBO J 24:4211–23
    [Google Scholar]
  113. 113.
    Shu X-Q, Llinas A, Mendell LM. 1999. Effects of trkB and trkC neurotrophin receptor agonists on thermal nociception: a behavioral and electrophysiological study. Pain 80:463–70
    [Google Scholar]
  114. 114.
    Bonnington JK, McNaughton PA. 2003. Signalling pathways involved in the sensitisation of mouse nociceptive neurones by nerve growth factor. J. Physiol. 551:433–46
    [Google Scholar]
  115. 115.
    Cao E, Cordero-Morales JF, Liu B, Qin F, Julius D 2013. TRPV1 channels are intrinsically heat sensitive and negatively regulated by phosphoinositide lipids. Neuron 77:667–79
    [Google Scholar]
  116. 116.
    Ufret-Vincenty CA, Klein RM, Collins MD, Rosasco MG, Martinez GQ, Gordon SE. 2015. Mechanism for phosphoinositide selectivity and activation of TRPV1 ion channels. J. Gen. Physiol. 145:431–42
    [Google Scholar]
  117. 117.
    Liu B, Zhang C, Qin F. 2005. Functional recovery from desensitization of vanilloid receptor TRPV1 requires resynthesis of phosphatidylinositol 4,5-bisphosphate. J. Neurosci. 25:4835–43
    [Google Scholar]
  118. 118.
    Rohacs T. 2015. Phosphoinositide regulation of TRPV1 revisited. Pflügers Arch. Eur. J. Physiol. 467:1851–69
    [Google Scholar]
  119. 119.
    Ufret-Vincenty CA, Klein RM, Hua L, Angueyra J, Gordon SE. 2011. Localization of the PIP2 sensor of TRPV1 ion channels. J. Biol. Chem. 286:9688–98
    [Google Scholar]
  120. 120.
    Hofmann T, Obukhov AG, Schaefer M, Harteneck C, Gudermann T, Schultz G. 1999. Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol. Nature 397:259–63
    [Google Scholar]
  121. 121.
    Bai Y, Yu X, Chen H, Horne D, White R et al. 2020. Structural basis for pharmacological modulation of the TRPC6 channel. eLife 9:e53311
    [Google Scholar]
/content/journals/10.1146/annurev-biochem-032620-105738
Loading
/content/journals/10.1146/annurev-biochem-032620-105738
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error