1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Physiology
  4. Volume 86, 2024
  5. Article

Annual Review of Physiology

Volume 86, 2024

Transcendent Aspects of Proton Channels

Abstract

A handful of biological proton-selective ion channels exist. Some open at positive or negative membrane potentials, others open at low or high pH, and some are light activated. This review focuses on common features that result from the unique properties of protons. Proton conduction through water or proteins differs qualitatively from that of all other ions. Extraordinary proton selectivity is needed to ensure that protons permeate and other ions do not. Proton selectivity arises from a proton pathway comprising a hydrogen-bonded chain that typically includes at least one titratable amino acid side chain. The enormously diverse functions of proton channels in disparate regions of the phylogenetic tree can be summarized by considering the chemical and electrical consequences of proton flux across membranes. This review discusses examples of cells in which proton efflux serves to increase pH, decrease pH, control the membrane potential, generate action potentials, or compensate transmembrane movement of electrical charge.

Keyword(s): HVCN1, ion channels, pH
Loading

Article metrics loading...

/content/journals/10.1146/annurev-physiol-042222-023242
2024-02-12
2024-04-27
Loading full text...

Full text loading...

/deliver/fulltext/physiol/86/1/annurev-physiol-042222-023242.html?itemId=/content/journals/10.1146/annurev-physiol-042222-023242&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Xu Y, Wu X, Hong JJ, Shin W, Ji X et al. 2021. The renaissance of proton batteries. Small Struct. 2:2000113
     [Google Scholar]
  2. 2.
    Elliott JA, Paddison SJ. 2007. Modelling of morphology and proton transport in PFSA membranes. Phys. Chem. Chem. Phys. 9:2602–18
     [Google Scholar]
  3. 3.
    Wu X, Hong JJ, Shin W et al. 2019. Diffusion-free Grotthuss topochemistry for high-rate and long-life proton batteries. Nat. Energy 4:123–30
     [Google Scholar]
  4. 4.
    Kreuer KD, Paddison SJ, Spohr E, Schuster M. 2004. Transport in proton conductors for fuel-cell applications: simulations, elementary reactions, and phenomenology. Chem. Rev. 104:4637–78
     [Google Scholar]
  5. 5.
    Hu M, Li P, Wang C, Feng X, Geng Q et al. 2022. Parkinson's disease-risk protein TMEM175 is a proton-activated proton channel in lysosomes. Cell 185:2292–308.e20
     [Google Scholar]
  6. 6.
    Chang RB, Waters H, Liman ER. 2010. A proton current drives action potentials in genetically identified sour taste cells. PNAS 107:22320–25
     [Google Scholar]
  7. 7.
    Tu YH, Cooper AJ, Teng B, Chang RB, Artiga DJ et al. 2018. An evolutionarily conserved gene family encodes proton-selective ion channels. Science 359:1047–50
     [Google Scholar]
  8. 8.
    Hurle B, Marques-Bonet T, Antonacci F, Hughes I, Ryan JF et al. 2011. Lineage-specific evolution of the vertebrate Otopetrin gene family revealed by comparative genomic analyses. BMC Evol. Biol. 11:23
     [Google Scholar]
  9. 9.
    Cherny VV, Markin VS, DeCoursey TE. 1995. The voltage-activated hydrogen ion conductance in rat alveolar epithelial cells is determined by the pH gradient. J. Gen. Physiol. 105:861–96
     [Google Scholar]
  10. 10.
    Bushman JD, Ye W, Liman ER. 2015. A proton current associated with sour taste: distribution and functional properties. FASEB J. 29:3014–26
     [Google Scholar]
  11. 11.
    Teng B, Kaplan JP, Liang Z, Krieger Z, Tu YH et al. 2022. Structural motifs for subtype-specific pH-sensitive gating of vertebrate otopetrin proton channels. eLife 11:e77946
     [Google Scholar]
  12. 12.
    Chang WW, Matt AS, Schewe M, Musinszki M, Grüssel S et al. 2021. An otopetrin family proton channel promotes cellular acid efflux critical for biomineralization in a marine calcifier. PNAS 118:e2101378118
     [Google Scholar]
  13. 13.
    Tian L, Zhang H, Yang S, Luo A, Kamau PM et al. 2023. Vertebrate OTOP1 is also an alkali-activated channel. Nat. Commun. 14:26
     [Google Scholar]
  14. 14.
    Teng B, Wilson CE, Tu YH, Joshi NR, Kinnamon SC, Liman ER. 2019. Cellular and neural responses to sour stimuli require the proton channel Otop1. Curr. Biol. 29:3647–56
     [Google Scholar]
  15. 15.
    Zhang J, Jin H, Zhang W, Ding C, O'Keeffe S et al. 2019. Sour sensing from the tongue to the brain. Cell 179:392–402
     [Google Scholar]
  16. 16.
    Chen Q, Zeng W, She J, Bai XC, Jiang Y. 2019. Structural and functional characterization of an otopetrin family proton channel. eLife 8:e46710
     [Google Scholar]
  17. 17.
    Saotome K, Teng B, Tsui CCA, Lee WH, Tu YH et al. 2019. Structures of the otopetrin proton channels Otop1 and Otop3. Nat. Struct. Mol. Biol. 26:518–25
     [Google Scholar]
  18. 18.
    Teng B, Kaplan JP, Liang Z, Goldschen-Ohm M, Liman ER. 2023. Zinc activation of OTOP proton channels identifies structural elements of the gating apparatus. eLife 12:e85317
     [Google Scholar]
  19. 19.
    Li B, Wang Y, Castro A, Ng C, Wang Z et al. 2022. The roles of two extracellular loops in proton sensing and permeation in human Otop1 proton channel. Commun. Biol. 5:1110
     [Google Scholar]
  20. 20.
    Nagel G, Ollig D, Fuhrmann M, Kateriya S, Musti AM et al. 2002. Channelrhodopsin-1: a light-gated proton channel in green algae. Science 296:2395–98
     [Google Scholar]
  21. 21.
    Lanyi JK. 2006. Proton transfers in the bacteriorhodopsin photocycle. Biochim. Biophys. Acta 1757:1012–18
     [Google Scholar]
  22. 22.
    Eisenhauer K, Kuhne J, Ritter E, Berndt A, Wolf S et al. 2012. In channelrhodopsin-2 Glu-90 is crucial for ion selectivity and is deprotonated during the photocycle. J. Biol. Chem. 287:6904–11
     [Google Scholar]
  23. 23.
    Wobig L, Wolfenstetter T, Fechner S, Bonigk W, Korschen HG et al. 2020. A family of hyperpolarization-activated channels selective for protons. PNAS 117:13783–91
     [Google Scholar]
  24. 24.
    Liu B, Carlson RJ, Pires IS, Gentili M, Feng E et al. 2023. Human STING is a proton channel. Science 381:508–14
     [Google Scholar]
  25. 25.
    Holsinger LJ, Nichani D, Pinto LH, Lamb RA. 1994. Influenza A virus M2 ion channel protein: a structure-function analysis. J. Virol. 68:1551–63
     [Google Scholar]
  26. 26.
    Pinto LH, Dieckmann GR, Gandhi CS, Papworth CG, Braman J et al. 1997. A functionally defined model for the M2 proton channel of influenza A virus suggests a mechanism for its ion selectivity. PNAS 94:11301–6
     [Google Scholar]
  27. 27.
    Pinto LH, Holsinger LJ, Lamb RA. 1992. Influenza virus M2 protein has ion channel activity. Cell 69:517–28
     [Google Scholar]
  28. 28.
    Wang C, Lamb RA, Pinto LH. 1995. Activation of the M2 ion channel of influenza virus: a role for the transmembrane domain histidine residue. Biophys. J. 69:1363–71
     [Google Scholar]
  29. 29.
    Hu F, Schmidt-Rohr K, Hong M. 2012. NMR detection of pH-dependent histidine-water proton exchange reveals the conduction mechanism of a transmembrane proton channel. J. Am. Chem. Soc. 134:3703–13
     [Google Scholar]
  30. 30.
    Nair SK, Christianson DW. 1991. Unexpected pH-dependent conformation of His-64, the proton shuttle of carbonic anhydrase. J. Am. Chem. Soc. 113:9455–58
     [Google Scholar]
  31. 31.
    Silverman DN, Lindskog S. 1988. The catalytic mechanism of carbonic anhydrase: Implications of a rate-limiting protolysis of water. Acc. Chem. Res. 21:30–36
     [Google Scholar]
  32. 32.
    Chaves G, Ayuyan AG, Cherny VV, Morgan D, Franzen A et al. 2023. Unexpected expansion of the voltage-gated proton channel family. FEBS J 290:1008–26
     [Google Scholar]
  33. 33.
    Chaves G, Jardin C, Franzen A, Mahorivska I, Musset B, Derst C. 2023. Proton channels in molluscs: a new bivalvian-specific minimal HV4 channel. FEBS J. 290:3436–47
     [Google Scholar]
  34. 34.
    DeCoursey TE. 2003. Voltage-gated proton channels and other proton transfer pathways. Physiol. Rev. 83:475–579
     [Google Scholar]
  35. 35.
    DeCoursey TE, Cherny VV. 1994. Voltage-activated hydrogen ion currents. J. Membr. Biol. 141:203–23
     [Google Scholar]
  36. 36.
    Carmona EM, Fernandez M, Alvear-Arias JJ, Neely A, Larsson HP et al. 2021. The voltage sensor is responsible for ΔpH dependence in HV1 channels. PNAS 118:e2025556118
     [Google Scholar]
  37. 37.
    Villalba-Galea CA. 2014. Hv1 proton channel opening is preceded by a voltage-independent transition. Biophys. J. 107:1564–72
     [Google Scholar]
  38. 38.
    Han S, Peng S, Vance J, Tran K, Do N et al. 2022. Structural dynamics determine voltage and pH gating in human voltage-gated proton channel. eLife 11:e73093
     [Google Scholar]
  39. 39.
    Sokolov VS, Cherny VV, Ayuyan AG, DeCoursey TE. 2021. Analysis of an electrostatic mechanism for ΔpH dependent gating of the voltage-gated proton channel, HV1, supports a contribution of protons to gating charge. Biochim. Biophys. Acta Bioenerg. 1862:148480
     [Google Scholar]
  40. 40.
    Jardin C, Ohlwein N, Franzen A, Chaves G, Musset B. 2022. The pH-dependent gating of the human voltage-gated proton channel from computational simulations. Phys. Chem. Chem. Phys. 24:9964–77
     [Google Scholar]
  41. 41.
    Byerly L, Meech R, Moody W Jr. 1984. Rapidly activating hydrogen ion currents in perfused neurones of the snail, Lymnaea stagnalis. J. Physiol. 351:199–216
     [Google Scholar]
  42. 42.
    Fogel M, Hastings JW. 1972. Bioluminescence: mechanism and mode of control of scintillon activity. PNAS 69:690–93
     [Google Scholar]
  43. 43.
    Rodriguez JD, Haq S, Bachvaroff T, Nowak KF, Nowak SJ et al. 2017. Identification of a vacuolar proton channel that triggers the bioluminescent flash in dinoflagellates. PLOS ONE 12:e0171594
     [Google Scholar]
  44. 44.
    Smith SM, Morgan D, Musset B, Cherny VV, Place AR et al. 2011. Voltage-gated proton channel in a dinoflagellate. PNAS 108:18162–67
     [Google Scholar]
  45. 45.
    Taylor AR, Chrachri A, Wheeler G, Goddard H, Brownlee C. 2011. A voltage-gated H+ channel underlying pH homeostasis in calcifying coccolithophores. PLOS Biol 9:e1001085
     [Google Scholar]
  46. 46.
    Rangel-Yescas G, Cervantes C, Cervantes-Rocha MA, Suarez-Delgado E, Banaszak AT et al. 2021. Discovery and characterization of HV1-type proton channels in reef-building corals. eLife 10:e69248
     [Google Scholar]
  47. 47.
    Kottmeier DM, Chrachri A, Langer G, Helliwell KE, Wheeler GL, Brownlee C. 2022. Reduced H+ channel activity disrupts pH homeostasis and calcification in coccolithophores at low ocean pH. PNAS 119:e2118009119
     [Google Scholar]
  48. 48.
    von Dassow P. 2022. Voltage-gated proton channels explain coccolithophore sensitivity to ocean acidification. PNAS 119:e2206426119
     [Google Scholar]
  49. 49.
    Henderson LM, Chappell JB, Jones OT. 1987. The superoxide-generating NADPH oxidase of human neutrophils is electrogenic and associated with an H+ channel. Biochem. J 246:325–29
     [Google Scholar]
  50. 50.
    DeCoursey TE, Morgan D, Cherny VV. 2003. The voltage dependence of NADPH oxidase reveals why phagocytes need proton channels. Nature 422:531–34
     [Google Scholar]
  51. 51.
    Schrenzel J, Serrander L, Bánfi B, Nüsse O, Fouyouzi R et al. 1998. Electron currents generated by the human phagocyte NADPH oxidase. Nature 392:734–37
     [Google Scholar]
  52. 52.
    Murphy R, DeCoursey TE. 2006. Charge compensation during the phagocyte respiratory burst. Biochim. Biophys. Acta 1757:996–1011
     [Google Scholar]
  53. 53.
    Morgan D, Capasso M, Musset B, Cherny VV, Ríos E et al. 2009. Voltage-gated proton channels maintain pH in human neutrophils during phagocytosis. PNAS 106:18022–27
     [Google Scholar]
  54. 54.
    Iovannisci D, Illek B, Fischer H. 2010. Function of the HVCN1 proton channel in airway epithelia and a naturally occurring mutation, M91T. J. Gen. Physiol. 136:35–46
     [Google Scholar]
  55. 55.
    Lishko PV, Botchkina IL, Fedorenko A, Kirichok Y. 2010. Acid extrusion from human spermatozoa is mediated by flagellar voltage-gated proton channel. Cell 140:327–37
     [Google Scholar]
  56. 56.
    Musset B, Clark RA, DeCoursey TE, Petheo GL, Geiszt M et al. 2012. NOX5 in human spermatozoa: expression, function, and regulation. J. Biol. Chem. 287:9376–88
     [Google Scholar]
  57. 57.
    Smith RY, Morgan D, Sharma L, Cherny VV, Tidswell N et al. 2019. Voltage-gated proton channels exist in the plasma membrane of human oocytes. Hum. Reprod. 34:1974–83
     [Google Scholar]
  58. 58.
    Pang H, Wang X, Zhao S, Xi W, Lv J et al. 2020. Loss of the voltage-gated proton channel Hv1 decreases insulin secretion and leads to hyperglycemia and glucose intolerance in mice. J. Biol. Chem. 295:3601–13
     [Google Scholar]
  59. 59.
    de Grotthuss CJT. 1806. Memoir on the decomposition of water and of the bodies that it holds in solution by means of galvanic electricity, transl. R Pomès, 2006. Biochim. Biophys. Acta 1757:871–75 (from French)
    [Google Scholar]
  60. 60.
    de Grotthuss CJT. 1806. Mémoire sur la décomposition de l'eau et des corps qu'elle tient en dissolution à l'aide de l'électricité galvanique. Ann. Chim. 58:54–74
     [Google Scholar]
  61. 61.
    Danneel H. 1905. Notiz über Ionengeschwindigkeiten. Z. Elektrochem. Angew. Phys. Chem. 11:249–52
     [Google Scholar]
  62. 62.
    Huggins ML. 1931. The role of hydrogen bonds in conduction by hydrogen and hydroxyl ions. J. Am. Chem. Soc. 53:3190–91
     [Google Scholar]
  63. 63.
    Eigen M. 1964. Proton transfer, acid-base catalysis, and enzymatic hydrolysis. Part I. Elementary processes. Angew. Chem. Int. Ed. 3:1–19
     [Google Scholar]
  64. 64.
    Lengyel S, Conway BE 1983. Proton solvation and proton transfer in chemical and electrochemical processes. Thermodynamic and Transport Properties of Aqueous and Molten Electrolytes BE Conway, JOM Bockris, E Yeager 339–98 New York: Plenum
     [Google Scholar]
  65. 65.
    Nagle JF, Morowitz HJ. 1978. Molecular mechanisms for proton transport in membranes. PNAS 75:298–302
     [Google Scholar]
  66. 66.
    Nagle JF, Tristram-Nagle S. 1983. Hydrogen bonded chain mechanisms for proton conduction and proton pumping. J. Membr. Biol. 74:1–14
     [Google Scholar]
  67. 67.
    Agmon N. 1995. The Grotthuss mechanism. Chem. Phys. Lett. 244:456–62
     [Google Scholar]
  68. 68.
    Tuckerman M, Laasonen K, Sprik M, Parrinello M. 1995. Ab initio molecular dynamics simulation of the solvation and transport of H3O+ and OH− ions in water. J. Phys. Chem. 99:5749–52
     [Google Scholar]
  69. 69.
    Levitt DG, Elias SR, Hautman JM. 1978. Number of water molecules coupled to the transport of sodium, potassium and hydrogen ions via gramicidin, nonactin or valinomycin. Biochim. Biophys. Acta 512:436–51
     [Google Scholar]
  70. 70.
    Rosenberg PA, Finkelstein A. 1978. Interaction of ions and water in gramicidin A channels: streaming potentials across lipid bilayer membranes. J. Gen. Physiol. 72:327–40
     [Google Scholar]
  71. 71.
    Wallace BA, Ravikumar K. 1988. The gramicidin pore: crystal structure of a cesium complex. Science 241:182–87
     [Google Scholar]
  72. 72.
    Myers VB, Haydon DA. 1972. Ion transfer across lipid membranes in the presence of gramicidin A. II. The ion selectivity. Biochim. Biophys. Acta 274:313–22
     [Google Scholar]
  73. 73.
    Cukierman S. 2000. Proton mobilities in water and in different stereoisomers of covalently linked gramicidin A channels. Biophys. J. 78:1825–34
     [Google Scholar]
  74. 74.
    Hall JE. 1975. Access resistance of a small circular pore. J. Gen. Physiol. 66:531–32
     [Google Scholar]
  75. 75.
    Decker ER, Levitt DG. 1988. Use of weak acids to determine the bulk diffusion limitation of H+ ion conductance through the gramicidin channel. Biophys. J. 53:25–32
     [Google Scholar]
  76. 76.
    Andersen OS. 1983. Ion movement through gramicidin A channels. Interfacial polarization effects on single-channel current measurements. Biophys. J. 41:135–46
     [Google Scholar]
  77. 77.
    Dani JA. 1986. Ion-channel entrances influence permeation. Net charge, size, shape, and binding considerations. Biophys. J. 49:607–18
     [Google Scholar]
  78. 78.
    Jordan PC. 1987. How pore mouth charge distributions alter the permeability of transmembrane ionic channels. Biophys. J. 51:297–311
     [Google Scholar]
  79. 79.
    Boytsov D, Brescia S, Chaves G, Koefler S, Hannesschlaeger C et al. 2023. Trapped pore waters in the open proton channel HV1. Small 19:e2205968
     [Google Scholar]
  80. 80.
    Haines TH. 1983. Anionic lipid headgroups as a proton-conducting pathway along the surface of membranes: a hypothesis. PNAS 80:160–64
     [Google Scholar]
  81. 81.
    Gutman M, Nachliel E. 1997. Time-resolved dynamics of proton transfer in proteinous systems. Annu. Rev. Phys. Chem. 48:329–56
     [Google Scholar]
  82. 82.
    Marantz Y, Nachliel E, Aagaard A, Brzezinski P, Gutman M. 1998. The proton collecting function of the inner surface of cytochrome c oxidase from Rhodobacter sphaeroides. PNAS 95:8590–95
     [Google Scholar]
  83. 83.
    Musset B, Cherny VV, Morgan D, Okamura Y, Ramsey IS et al. 2008. Detailed comparison of expressed and native voltage-gated proton channel currents. J. Physiol. 586:2477–86
     [Google Scholar]
  84. 84.
    De-la-Rosa V, Suárez-Delgado E, Rangel-Yescas GE, Islas LD. 2016. Currents through Hv1 channels deplete protons in their vicinity. J. Gen. Physiol. 147:127–36
     [Google Scholar]
  85. 85.
    DeCoursey TE. 1991. Hydrogen ion currents in rat alveolar epithelial cells. Biophys. J. 60:1243–53
     [Google Scholar]
  86. 86.
    Cherny VV, Murphy R, Sokolov V, Levis RA, DeCoursey TE. 2003. Properties of single voltage-gated proton channels in human eosinophils estimated by noise analysis and by direct measurement. J. Gen. Physiol. 121:615–28
     [Google Scholar]
  87. 87.
    DeCoursey TE, Cherny VV. 1996. Effects of buffer concentration on voltage-gated H+ currents: Does diffusion limit the conductance?. Biophys. J. 71:182–93
     [Google Scholar]
  88. 88.
    DeCoursey TE, Hosler J. 2014. Philosophy of voltage-gated proton channels. J. R. Soc. Interface 11:20130799
     [Google Scholar]
  89. 89.
    Wraight CA. 2006. Chance and design—proton transfer in water, channels and bioenergetic proteins. Biochim. Biophys. Acta 1757:886–912
     [Google Scholar]
  90. 90.
    Hall JE, Freites JA, Tobias DJ. 2019. Experimental and simulation studies of aquaporin 0 water permeability and regulation. Chem. Rev. 119:6015–39
     [Google Scholar]
  91. 91.
    Wu B, Steinbronn C, Alsterfjord M, Zeuthen T, Beitz E. 2009. Concerted action of two cation filters in the aquaporin water channel. EMBO J. 28:2188–94
     [Google Scholar]
  92. 92.
    Tu CK, Silverman DN, Forsman C, Jonsson BH, Lindskog S. 1989. Role of histidine 64 in the catalytic mechanism of human carbonic anhydrase II studied with a site-specific mutant. Biochemistry 28:7913–18
     [Google Scholar]
  93. 93.
    Miller MJ, Oldenburg M, Fillingame RH. 1990. The essential carboxyl group in subunit c of the F1F0 ATP synthase can be moved and H+-translocating function retained. PNAS 87:4900–4
     [Google Scholar]
  94. 94.
    Blair DF, Berg HC. 1990. The MotA protein of E. coli is a proton-conducting component of the flagellar motor. Cell 60:439–49
     [Google Scholar]
  95. 95.
    Zhou J, Sharp LL, Tang HL, Lloyd SA, Billings S et al. 1998. Function of protonatable residues in the flagellar motor of Escherichia coli: a critical role for Asp 32 of MotB. J. Bacteriol. 180:2729–35
     [Google Scholar]
  96. 96.
    Grytsyk N, Sugihara J, Kaback HR, Hellwig P. 2017. pKa of Glu325 in LacY. PNAS 114:1530–35
     [Google Scholar]
  97. 97.
    Weinglass AB, Smirnova IN, Kaback HR. 2001. Engineering conformational flexibility in the lactose permease of Escherichia coli: use of glycine-scanning mutagenesis to rescue mutant Glu325→Asp. Biochemistry 40:769–76
     [Google Scholar]
  98. 98.
    Wietek J, Wiegert JS, Adeishvili N, Schneider F, Watanabe H et al. 2014. Conversion of channelrhodopsin into a light-gated chloride channel. Science 344:409–12
     [Google Scholar]
  99. 99.
    Henderson R, Baldwin JM, Ceska TA, Zemlin F, Beckmann E, Downing KH. 1990. Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopy. J. Mol. Biol. 213:899–929
     [Google Scholar]
  100. 100.
    Lanyi JK. 1995. Bacteriorhodopsin as a model for proton pumps. Nature 375:461–63
     [Google Scholar]
  101. 101.
    Ädelroth P, Paddock ML, Tehrani A, Beatty JT, Feher G, Okamura MY. 2001. Identification of the proton pathway in bacterial reaction centers: decrease of proton transfer rate by mutation of surface histidines at H126 and H128 and chemical rescue by imidazole identifies the initial proton donors. Biochemistry 40:14538–46
     [Google Scholar]
  102. 102.
    Paddock ML, Ädelroth P, Chang C, Abresch EC, Feher G, Okamura MY. 2001. Identification of the proton pathway in bacterial reaction centers: cooperation between Asp-M17 and Asp-L210 facilitates proton transfer to the secondary quinone (QB). Biochemistry 40:6893–902
     [Google Scholar]
  103. 103.
    Paddock ML, Feher G, Okamura MY. 2003. Proton transfer pathways and mechanism in bacterial reaction centers. FEBS Lett. 555:45–50
     [Google Scholar]
  104. 104.
    Fetter JR, Qian J, Shapleigh J, Thomas JW, Garcia-Horsman A et al. 1995. Possible proton relay pathways in cytochrome c oxidase. PNAS 92:1604–8
     [Google Scholar]
  105. 105.
    Smirnova IA, Ädelroth P, Gennis RB, Brzezinski P. 1999. Aspartate-132 in cytochrome c oxidase from Rhodobacter sphaeroides is involved in a two-step proton transfer during oxo-ferryl formation. Biochemistry 38:6826–33
     [Google Scholar]
  106. 106.
    Brändén M, Tomson F, Gennis RB, Brzezinski P. 2002. The entry point of the K-proton-transfer pathway in cytochrome c oxidase. Biochemistry 41:10794–98
     [Google Scholar]
  107. 107.
    Ramsey IS, Mokrab Y, Carvacho I, Sands ZA, Sansom MSP, Clapham DE. 2010. An aqueous H+ permeation pathway in the voltage-gated proton channel Hv1. Nat. Struct. Mol. Biol. 17:869–75
     [Google Scholar]
  108. 108.
    Randa HS, Forrest LR, Voth GA, Sansom MS. 1999. Molecular dynamics of synthetic leucine-serine ion channels in a phospholipid membrane. Biophys. J. 77:2400–10
     [Google Scholar]
  109. 109.
    Bennett AL, Ramsey IS. 2017. CrossTalk opposing view: proton transfer in HV1 utilizes a water wire, and does not require transient protonation of a conserved aspartate in the S1 transmembrane helix. J. Physiol. 595:6797–99
     [Google Scholar]
  110. 110.
    Lear JD, Wasserman ZR, DeGrado WF. 1988. Synthetic amphiphilic peptide models for protein ion channels. Science 240:1177–81
     [Google Scholar]
  111. 111.
    Kratochvil HT, Watkins LC, Mravic M, Thomaston JL, Nicoludis JM et al. 2023. Transient water wires mediate selective proton transport in designed channel proteins. Nat. Chem. 15:1012–21
     [Google Scholar]
  112. 112.
    Wu Y, Ilan B, Voth GA. 2007. Charge delocalization in proton channels, II: the synthetic LS2 channel and proton selectivity. Biophys. J. 92:61–69
     [Google Scholar]
  113. 113.
    Jiang T, Hall A, Eres M, Hemmatian Z, Qiao B et al. 2020. Single-chain heteropolymers transport protons selectively and rapidly. Nature 577:216–20
     [Google Scholar]
  114. 114.
    Otake KI, Otsubo K, Komatsu T, Dekura S, Taylor JM et al. 2020. Confined water-mediated high proton conduction in hydrophobic channel of a synthetic nanotube. Nat. Commun. 11:843
     [Google Scholar]
  115. 115.
    Kulleperuma K, Smith SM, Morgan D, Musset B, Holyoake J et al. 2013. Construction and validation of a homology model of the human voltage-gated proton channel hHV1. J. Gen. Physiol. 141:445–65
     [Google Scholar]
  116. 116.
    DeCoursey TE, Morgan D, Musset B, Cherny VV. 2016. Insights into the structure and function of HV1 from a meta-analysis of mutation studies. J. Gen. Physiol. 148:97–118
     [Google Scholar]
  117. 117.
    Musset B, Smith SM, Rajan S, Morgan D, Cherny VV, DeCoursey TE. 2011. Aspartate112 is the selectivity filter of the human voltage-gated proton channel. Nature 480:273–77
     [Google Scholar]
  118. 118.
    Chamberlin A, Qiu F, Wang Y, Noskov SY, Larsson HP. 2015. Mapping the gating and permeation pathways in the voltage-gated proton channel Hv1. J. Mol. Biol. 427:131–45
     [Google Scholar]
  119. 119.
    Chaves G, Derst C, Franzen A, Mashimo Y, Machida R, Musset B. 2016. Identification of an HV1 voltage-gated proton channel in insects. FEBS J 283:1453–64
     [Google Scholar]
  120. 120.
    Chaves G, Derst C, Jardin C, Franzen A, Musset B. 2022. Voltage-gated proton channels in polyneopteran insects. FEBS Open Bio 12:523–37
     [Google Scholar]
  121. 121.
    DeCoursey TE. 2015. The voltage-gated proton channel: a riddle, wrapped in a mystery, inside an enigma. Biochemistry 54:3250–68
     [Google Scholar]
  122. 122.
    Morgan D, Musset B, Kulleperuma K, Smith SM, Rajan S et al. 2013. Peregrination of the selectivity filter delineates the pore of the human voltage-gated proton channel hHV1. J. Gen. Physiol. 142:625–40
     [Google Scholar]
  123. 123.
    Chamberlin A, Qiu F, Rebolledo S, Wang Y, Noskov SY, Larsson HP. 2014. Hydrophobic plug functions as a gate in voltage-gated proton channels. PNAS 111:E273–82
     [Google Scholar]
  124. 124.
    Gianti E, Delemotte L, Klein ML, Carnevale V. 2016. On the role of water density fluctuations in the inhibition of a proton channel. PNAS 113:E8359–68
     [Google Scholar]
  125. 125.
    van Keulen SC, Gianti E, Carnevale V, Klein ML, Rothlisberger U, Delemotte L. 2017. Does proton conduction in the voltage-gated H+ channel hHv1 involve Grotthuss-like hopping via acidic residues?. J. Phys. Chem. B. 121:3340–51
     [Google Scholar]
  126. 126.
    Lee M, Bai C, Feliks M, Alhadeff R, Warshel A. 2018. On the control of the proton current in the voltage-gated proton channel Hv1. PNAS 115:10321–26
     [Google Scholar]
  127. 127.
    Dudev T, Musset B, Morgan D, Cherny VV, Smith SM et al. 2015. Selectivity mechanism of the voltage-gated proton channel, HV1. Sci. Rep. 5:10320
     [Google Scholar]
  128. 128.
    Kaback HR. 2015. A chemiosmotic mechanism of symport. PNAS 112:1259–64
     [Google Scholar]
  129. 129.
    Vierock J, Grimm C, Nitzan N, Hegemann P. 2017. Molecular determinants of proton selectivity and gating in the red-light activated channelrhodopsin Chrimson. Sci. Rep. 7:9928
     [Google Scholar]
  130. 130.
    Liang R, Swanson JMJ, Madsen JJ, Hong M, DeGrado WF, Voth GA. 2016. Acid activation mechanism of the influenza A M2 proton channel. PNAS 113:E6955–64
     [Google Scholar]
  131. 131.
    DeCoursey TE. 2018. Voltage and pH sensing by the voltage-gated proton channel, HV1. J. R. Soc. Interface 15:20180108
     [Google Scholar]
  132. 132.
    Morgan D, Cherny VV, Murphy R, Katz BZ, DeCoursey TE. 2005. The pH dependence of NADPH oxidase in human eosinophils. J. Physiol. 569:419–31
     [Google Scholar]
  133. 133.
    Musset B, Morgan D, Cherny VV, MacGlashan DW Jr., Thomas LL et al. 2008. A pH-stabilizing role of voltage-gated proton channels in IgE-mediated activation of human basophils. PNAS 105:11020–25
     [Google Scholar]
  134. 134.
    Thomas RC. 1988. Changes in the surface pH of voltage-clamped snail neurones apparently caused by H+ fluxes through a channel. J. Physiol. 398:313–27
     [Google Scholar]
  135. 135.
    El Chemaly A, Nunes P, Jimaja W, Castelbou C, Demaurex N. 2014. Hv1 proton channels differentially regulate the pH of neutrophil and macrophage phagosomes by sustaining the production of phagosomal ROS that inhibit the delivery of vacuolar ATPases. J. Leukoc. Biol. 95:827–39
     [Google Scholar]
  136. 136.
    Fischer H. 2012. Function of proton channels in lung epithelia. Wiley Interdiscip. Rev. Membr. Transp. Signal 1:247–58
     [Google Scholar]
  137. 137.
    Ma J, Gao X, Li Y, DeCoursey TE, Shull GE, Wang HS. 2022. The HVCN1 voltage-gated proton channel contributes to pH regulation in canine ventricular myocytes. J. Physiol. 600:2089–103
     [Google Scholar]
  138. 138.
    Vairamani K, Wang HS, Medvedovic M, Lorenz JN, Shull GE. 2017. RNA SEQ analysis indicates that the AE3 Cl−/HCO3− exchanger contributes to active transport-mediated CO2 disposal in heart. Sci. Rep. 7:7264
     [Google Scholar]
  139. 139.
    DeCoursey TE. 2000. Hypothesis: Do voltage-gated H+ channels in alveolar epithelial cells contribute to CO2 elimination by the lung?. Am. J. Physiol. Cell Physiol. 278:C1–10
     [Google Scholar]
  140. 140.
    Petho Z, Najder K, Carvalho T, McMorrow R, Todesca LM et al. 2020. pH-channeling in cancer: how pH-dependence of cation channels shapes cancer pathophysiology. Cancers 12:2484
     [Google Scholar]
  141. 141.
    Warburg O. 1956. On the origin of cancer cells. Science 123:309–14
     [Google Scholar]
  142. 142.
    Hondares E, Brown MA, Musset B, Morgan D, Cherny VV et al. 2014. Enhanced activation of an amino-terminally truncated isoform of the voltage-gated proton channel HVCN1 enriched in malignant B cells. PNAS 111:18078–83
     [Google Scholar]
  143. 143.
    Bare DJ, Cherny VV, DeCoursey TE, Abukhdeir AM, Morgan D. 2020. Expression and function of voltage gated proton channels (HV1) in MDA-MB-231 cells. PLOS ONE 15:e0227522
     [Google Scholar]
  144. 144.
    El Chemaly A, Jaquet V, Cambet Y, Caillon A, Cherpin O et al. 2023. Discovery and validation of new Hv1 proton channel inhibitors with onco-therapeutic potential. Biochim. Biophys. Acta Mol. Cell Res. 1870:119415
     [Google Scholar]
  145. 145.
    Wang Y, Li SJ, Wu X, Che Y, Li Q. 2012. Clinicopathological and biological significance of human voltage-gated proton channel Hv1 protein overexpression in breast cancer. J. Biol. Chem. 287:13877–88
     [Google Scholar]
  146. 146.
    Wang Y, Wu X, Li Q, Zhang S, Li SJ. 2013. Human voltage-gated proton channel HV1: a new potential biomarker for diagnosis and prognosis of colorectal cancer. PLOS ONE 8:e70550
     [Google Scholar]
  147. 147.
    El Chemaly A, Okochi Y, Sasaki M, Arnaudeau S, Okamura Y, Demaurex N. 2010. VSOP/Hv1 proton channels sustain calcium entry, neutrophil migration, and superoxide production by limiting cell depolarization and acidification. J. Exp. Med. 207:129–39
     [Google Scholar]
  148. 148.
    Quatrefages A. 1850. Observations sur les noctiluques. Ann. Sci. Nat. Zool. Biol. Anim. 14:226–35
     [Google Scholar]
  149. 149.
    Schmitter RE, Njus D, Sulzman FM, Gooch VD, Hastings JW. 1976. Dinoflagellate bioluminescence: a comparative study of invitro components. J. Cell Physiol. 87:123–34
     [Google Scholar]
  150. 150.
    Eckert R, Reynolds GT. 1967. The subcellular origin of bioluminescence in Noctiluca miliaris. J. Gen. Physiol. 50:1429–58
     [Google Scholar]
  151. 151.
    Fogel M, Hastings JW. 1971. A substrate-binding protein in the Gonyaulax bioluminescence reaction. Arch. Biochem. Biophys. 142:310–21
     [Google Scholar]
  152. 152.
    Hastings JW, Vergin M, DeSa R 1966. Scintillons: the biochemistry of dinoflagellate bioluminescence. Bioluminescence in Progress FH Johnson, Y Haneda 301–29 Princeton, NJ: Princeton Univ. Press
     [Google Scholar]
  153. 153.
    Krieger N, Hastings JW. 1968. Bioluminescence: pH activity profiles of related luciferase fractions. Science 161:586–89
     [Google Scholar]
  154. 154.
    Chang JJ. 1960. Electrophysiological studies of a non-luminescent form of the dinoflagellate Noctiluca miliaris. J. Cell Comp. Physiol. 56:33–42
     [Google Scholar]
  155. 155.
    Eckert R, Sibaoka T. 1968. The flash-triggering action potential of the luminescent dinoflagellate Noctiluca. J. Gen. Physiol. 52:258–82
     [Google Scholar]
  156. 156.
    Nawata T, Sibaoka T. 1976. Ionic composition and pH of the vacuolar sap in marine dinoflagellate Noctiluca. Plant Cell Physiol 17:265–72
     [Google Scholar]
  157. 157.
    Nicolas MT, Nicolas G, Johnson CH, Bassot JM, Hastings JW. 1987. Characterization of the bioluminescent organelles in Gonyaulax polyedra (dinoflagellates) after fast-freeze fixation and antiluciferase immunogold staining. J. Cell Biol. 105:723–35
     [Google Scholar]
  158. 158.
    Zhao C, Tombola F. 2021. Voltage-gated proton channels from fungi highlight role of peripheral regions in channel activation. Commun. Biol. 4:261
     [Google Scholar]
  159. 159.
    Geiszt M, Kapus A, Nemet K, Farkas L, Ligeti E. 1997. Regulation of capacitative Ca2+ influx in human neutrophil granulocytes. Alterations in chronic granulomatous disease. J. Biol. Chem. 272:26471–78
     [Google Scholar]
  160. 160.
    Jankowski A, Grinstein S. 1999. A noninvasive fluorimetric procedure for measurement of membrane potential. Quantification of the NADPH oxidase-induced depolarization in activated neutrophils. J. Biol. Chem. 274:26098–104
     [Google Scholar]
  161. 161.
    Rada BK, Geiszt M, Káldi K, Tímár C, Ligeti E. 2004. Dual role of phagocytic NADPH oxidase in bacterial killing. Blood 104:2947–53
     [Google Scholar]
  162. 162.
    DeCoursey TE. 2003. Interactions between NADPH oxidase and voltage-gated proton channels: why electron transport depends on proton transport. FEBS Lett 555:57–61
     [Google Scholar]
  163. 163.
    Musset B, Cherny VV, Morgan D, DeCoursey TE. 2009. The intimate and mysterious relationship between proton channels and NADPH oxidase. FEBS Lett. 583:7–12
     [Google Scholar]
  164. 164.
    Capasso M, Bhamrah MK, Henley T, Boyd RS, Langlais C et al. 2010. HVCN1 modulates BCR signal strength via regulation of BCR-dependent generation of reactive oxygen species. Nat. Immunol. 11:265–72
     [Google Scholar]
  165. 165.
    Fudim R, Szczepek M, Vierock J, Vogt A, Schmidt A et al. 2019. Design of a light-gated proton channel based on the crystal structure of Coccomyxa rhodopsin. Sci. Signal 12:eaav4203
     [Google Scholar]
  166. 166.
    Starace DM, Bezanilla F. 2001. Histidine scanning mutagenesis of basic residues of the S4 segment of the Shaker K+ channel. J. Gen. Physiol. 117:469–90
     [Google Scholar]
  167. 167.
    DeCoursey TE. 2010. Voltage-gated proton channels find their dream job managing the respiratory burst in phagocytes. Physiol. 25:27–40
     [Google Scholar]
  168. 168.
    Thomas RC, Meech RW. 1982. Hydrogen ion currents and intracellular pH in depolarized voltage-clamped snail neurones. Nature 299:826–28
     [Google Scholar]
  169. 169.
    Takeshita K, Sakata S, Yamashita E, Fujiwara Y, Kawanabe A et al. 2014. X-ray crystal structure of voltage-gated proton channel. Nat. Struct. Mol. Biol. 21:352–57
     [Google Scholar]
  170. 170.
    Schnell JR, Chou JJ. 2008. Structure and mechanism of the M2 proton channel of influenza A virus. Nature 451:591–95
     [Google Scholar]
  171. 171.
    Stouffer AL, Acharya R, Salom D, Levine AS, Di Costanzo L et al. 2008. Structural basis for the function and inhibition of an influenza virus proton channel. Nature 451:596–99
     [Google Scholar]
  172. 172.
    Teng B, Kaplan JP, Liang Z, Chyung KS, Goldschen-Ohm MP, Liman ER. 2023. Zinc activation of OTOP proton channels identifies structural elements of the gating apparatus. eLife 12:e85317
     [Google Scholar]
  173. 173.
    Kato HE, Zhang F, Yizhar O, Ramakrishnan C, Nishizawa T et al. 2012. Crystal structure of the channelrhodopsin light-gated cation channel. Nature 482:369–74
     [Google Scholar]
  174. 174.
    Brunner JD, Jakob RP, Schulze T, Neldner Y, Moroni A et al. 2020. Structural basis for ion selectivity in TMEM175 K+ channels. eLife 9:e53683
     [Google Scholar]
  175. 175.
    Lee C, Guo J, Zeng W, Kim S, She J et al. 2017. The lysosomal potassium channel TMEM175 adopts a novel tetrameric architecture. Nature 547:472–75
     [Google Scholar]
  176. 176.
    DeCoursey TE. 2013. Voltage-gated proton channels: molecular biology, physiology, and pathophysiology of the HV family. Physiol. Rev. 93:599–652
     [Google Scholar]
  177. 177.
    Ramsey IS, Moran MM, Chong JA, Clapham DE. 2006. A voltage-gated proton-selective channel lacking the pore domain. Nature 440:1213–16
     [Google Scholar]
  178. 178.
    Sasaki M, Takagi M, Okamura Y. 2006. A voltage sensor-domain protein is a voltage-gated proton channel. Science 312:589–92
     [Google Scholar]
  179. 179.
    Taylor AR, Brownlee C, Wheeler GL. 2012. Proton channels in algae: reasons to be excited. Trends Plant Sci 17:675–84
     [Google Scholar]
  180. 180.
    Sakata S, Miyawaki N, McCormack TJ, Arima H, Kawanabe A et al. 2016. Comparison between mouse and sea urchin orthologs of voltage-gated proton channel suggests role of S3 segment in activation gating. Biochim. Biophys. Acta 1858:2972–83
     [Google Scholar]
  181. 181.
    Kang BE, Baker BJ. 2016. Pado, a fluorescent protein with proton channel activity can optically monitor membrane potential, intracellular pH, and map gap junctions. Sci. Rep. 6:23865
     [Google Scholar]
  182. 182.
    Wright BJ, Bickham-Wright U, Yoshino TP, Jackson MB. 2017. H+ channels in embryonic Biomphalaria glabrata cell membranes: putative roles in snail host-schistosome interactions. PLOS Negl. Trop. Dis. 11:e0005467
     [Google Scholar]
  183. 183.
    Ratanayotha A, Kawai T, Higashijima SI, Okamura Y. 2017. Molecular and functional characterization of the voltage-gated proton channel in zebrafish neutrophils. Physiol. Rep. 5:e13345
     [Google Scholar]
  184. 184.
    Thomas S, Cherny VV, Morgan D, Artinian LR, Rehder V et al. 2018. Exotic properties of a voltage-gated proton channel from the snail Helisoma trivolvis. J. Gen. Physiol. 150:835–50
     [Google Scholar]
/content/journals/10.1146/annurev-physiol-042222-023242
Loading
Transcendent Aspects of Proton Channels
Annual Review of Physiology 86, 357 (2024); https://doi.org/10.1146/annurev-physiol-042222-023242
/content/journals/10.1146/annurev-physiol-042222-023242
/content/journals/10.1146/annurev-physiol-042222-023242
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

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