Abstract
Two-pore channels (TPCs) belong to the family of voltage-gated tetrameric cation channels and are ubiquitously expressed in organelles of animals and plants. These channels are believed to be evolutionary intermediates between homotetrameric voltage-gated potassium/sodium channels and the four-domain, single subunit, voltage-gated sodium/calcium channels. Each TPC subunit contains 12 transmembrane segments that can be divided into two homologous copies of an S1-S6 Shaker-like 6-TM domain. A functional TPC channel assembles as a dimer – the equivalent of a voltage-gated tetrameric cation channel. The plant TPC channel is localized in the vacuolar membrane and is also called the SV channel for generating the slow vacuolar (SV) current observed long before its molecular identification. Three subfamilies of mammalian TPC channels have been defined – TPC1, 2, and 3 – with the first two being ubiquitously expressed in animals and TPC3 being expressed in some animals but not in humans. Mammalian TPC1 and TPC2 are localized to the endolysosomal membrane and their functions are associated with various physiological processes. TPC3 is localized in the plasma membrane and its physiological function is not well defined.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ambrosio AL, Boyle JA, Aradi AE, Christian KA, Di Pietro SM (2016) TPC2 controls pigmentation by regulating melanosome pH and size. Proc Natl Acad Sci U S A 113:5622–5627. https://doi.org/10.1073/pnas.1600108113
Arndt L, Castonguay J, Arlt E, Meyer D, Hassan S, Borth H, Zierler S, Wennemuth G, Breit A, Biel M, Wahl-Schott C, Gudermann T, Klugbauer N, Boekhoff I (2014) NAADP and the two-pore channel protein 1 participate in the acrosome reaction in mammalian spermatozoa. Mol Biol Cell 25:948–964. https://doi.org/10.1091/mbc.E13-09-0523
Bellono NW, Escobar IE, Oancea E (2016) A melanosomal two-pore sodium channel regulates pigmentation. Sci Rep 6:26570. https://doi.org/10.1038/srep26570
Bonaventure G, Gfeller A, Proebsting WM, Hortensteiner S, Chetelat A, Martinoia E, Farmer EE (2007a) A gain-of-function allele of TPC1 activates oxylipin biogenesis after leaf wounding in Arabidopsis. Plant J 49:889–898. https://doi.org/10.1111/j.1365-313X.2006.03002.x
Bonaventure G, Gfeller A, Rodriguez VM, Armand F, Farmer EE (2007b) The fou2 gain-of-function allele and the wild-type allele of two pore channel 1 contribute to different extents or by different mechanisms to defense gene expression in Arabidopsis. Plant Cell Physiol 48:1775–1789. https://doi.org/10.1093/pcp/pcm151
Brailoiu E, Churamani D, Cai X, Schrlau MG, Brailoiu GC, Gao X, Hooper R, Boulware MJ, Dun NJ, Marchant JS, Patel S (2009) Essential requirement for two-pore channel 1 in NAADP-mediated calcium signaling. J Cell Biol 186:201–209. https://doi.org/10.1083/jcb.200904073
Calcraft PJ, Ruas M, Pan Z, Cheng X, Arredouani A, Hao X, Tang J, Rietdorf K, Teboul L, Chuang KT, Lin P, Xiao R, Wang C, Zhu Y, Lin Y, Wyatt CN, Parrington J, Ma J, Evans AM, Galione A, Zhu MX (2009) NAADP mobilizes calcium from acidic organelles through two-pore channels. Nature 459:596–600. https://doi.org/10.1038/nature08030
Cang C, Zhou Y, Navarro B, Seo YJ, Aranda K, Shi L, Battaglia-Hsu S, Nissim I, Clapham DE, Ren D (2013) mTOR regulates lysosomal ATP-sensitive two-pore Na(+) channels to adapt to metabolic state. Cell 152:778–790. https://doi.org/10.1016/j.cell.2013.01.023
Cang C, Bekele B, Ren D (2014) The voltage-gated sodium channel TPC1 confers endolysosomal excitability. Nat Chem Biol 10:463–469. https://doi.org/10.1038/nchembio.1522
Choi WG, Toyota M, Kim SH, Hilleary R, Gilroy S (2014) Salt stress-induced Ca2+ waves are associated with rapid, long-distance root-to-shoot signaling in plants. Proc Natl Acad Sci U S A 111:6497–6502. https://doi.org/10.1073/pnas.1319955111
Dadacz-Narloch B, Beyhl D, Larisch C, Lopez-Sanjurjo EJ, Reski R, Kuchitsu K, Muller TD, Becker D, Schonknecht G, Hedrich R (2011) A novel calcium binding site in the slow vacuolar cation channel TPC1 senses luminal calcium levels. Plant Cell 23:2696–2707. https://doi.org/10.1105/tpc.111.086751
Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R (1998) The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science 280:69–77
Favia A, Desideri M, Gambara G, D'Alessio A, Ruas M, Esposito B, Del Bufalo D, Parrington J, Ziparo E, Palombi F, Galione A, Filippini A (2014) VEGF-induced neoangiogenesis is mediated by NAADP and two-pore channel-2-dependent Ca2+ signaling. Proc Natl Acad Sci U S A 111:E4706–E4715. https://doi.org/10.1073/pnas.1406029111
Fernandez B, Fdez E, Gomez-Suaga P, Gil F, Molina-Villalba I, Ferrer I, Patel S, Churchill GC, Hilfiker S (2016) Iron overload causes endolysosomal deficits modulated by NAADP-regulated 2-pore channels and RAB7A. Autophagy 12:1487–1506. https://doi.org/10.1080/15548627.2016.1190072
Furuichi T, Cunningham KW, Muto S (2001) A putative two pore channel AtTPC1 mediates Ca(2+) flux in Arabidopsis leaf cells. Plant Cell Physiol 42:900–905
Grimm C, Holdt LM, Chen CC, Hassan S, Muller C, Jors S, Cuny H, Kissing S, Schroder B, Butz E, Northoff B, Castonguay J, Luber CA, Moser M, Spahn S, Lullmann-Rauch R, Fendel C, Klugbauer N, Griesbeck O, Haas A, Mann M, Bracher F, Teupser D, Saftig P, Biel M, Wahl-Schott C (2014) High susceptibility to fatty liver disease in two-pore channel 2-deficient mice. Nat Commun 5:4699. https://doi.org/10.1038/ncomms5699
Grimm C, Chen CC, Wahl-Schott C, Biel M (2017) Two-pore channels: catalyzers of endolysosomal transport and function. Front Pharmacol 8:45. https://doi.org/10.3389/fphar.2017.00045
Guo J, Zeng W, Chen Q, Lee C, Chen L, Yang Y, Cang C, Ren D, Jiang Y (2016) Structure of the voltage-gated two-pore channel TPC1 from Arabidopsis thaliana. Nature 531:196–201. https://doi.org/10.1038/nature16446
Guo J, Zeng W, Jiang Y (2017) Tuning the ion selectivity of two-pore channels. Proc Natl Acad Sci U S A 114:1009–1014. https://doi.org/10.1073/pnas.1616191114
Hedrich R, Marten I (2011) TPC1-SV channels gain shape. Mol Plant 4:428–441. https://doi.org/10.1093/mp/ssr017
Hedrich R, Neher E (1987) Cytoplasmic calcium regulates voltage-dependent ion channels in plant vacuoles. Nature 329:833–836. https://doi.org/10.1038/329833a0
Ishibashi K, Suzuki M, Imai M (2000) Molecular cloning of a novel form (two-repeat) protein related to voltage-gated sodium and calcium channels. Biochem Biophys Res Commun 270:370–376. https://doi.org/10.1006/bbrc.2000.2435
Jha A, Ahuja M, Patel S, Brailoiu E, Muallem S (2014) Convergent regulation of the lysosomal two-pore channel-2 by Mg(2)(+), NAADP, PI(3,5)P(2) and multiple protein kinases. EMBO J 33:501–511. https://doi.org/10.1002/embj.201387035
Kintzer AF, Stroud RM (2016) Structure, inhibition and regulation of two-pore channel TPC1 from Arabidopsis thaliana. Nature 531:258–262. https://doi.org/10.1038/nature17194
Lagostena L, Festa M, Pusch M, Carpaneto A (2017) The human two-pore channel 1 is modulated by cytosolic and luminal calcium. Sci Rep 7:43900. https://doi.org/10.1038/srep43900
Larisch N, Schulze C, Galione A, Dietrich P (2012) An N-terminal dileucine motif directs two-pore channels to the tonoplast of plant cells. Traffic 13:1012–1022. https://doi.org/10.1111/j.1600-0854.2012.01366.x
Long SB, Tao X, Campbell EB, MacKinnon R (2007) Atomic structure of a voltage-dependent K+ channel in a lipid membrane-like environment. Nature 450:376–382. https://doi.org/10.1038/nature06265
Patel S (2015) Function and dysfunction of two-pore channels. Sci Signal 8:re7. https://doi.org/10.1126/scisignal.aab3314
Payandeh J, Scheuer T, Zheng N, Catterall WA (2011) The crystal structure of a voltage-gated sodium channel. Nature 475:353–358. https://doi.org/10.1038/nature10238
Peiter E, Maathuis FJ, Mills LN, Knight H, Pelloux J, Hetherington AM, Sanders D (2005) The vacuolar Ca2+−activated channel TPC1 regulates germination and stomatal movement. Nature 434:404–408. https://doi.org/10.1038/nature03381
Pereira GJ, Hirata H, Fimia GM, do Carmo LG, Bincoletto C, Han SW, Stilhano RS, Ureshino RP, Bloor-Young D, Churchill G, Piacentini M, Patel S, Smaili SS (2011) Nicotinic acid adenine dinucleotide phosphate (NAADP) regulates autophagy in cultured astrocytes. J Biol Chem 286:27875–27881. https://doi.org/10.1074/jbc.C110.216580
Pitt SJ, Lam AKM, Rietdorf K, Galione A, Sitsapesan R (2014) Reconstituted human TPC1 is a proton-permeable ion channel and is activated by NAADP or Ca2+. Sci Signal 7:ra46. https://doi.org/10.1126/scisignal.2004854
Rahman T, Cai X, Brailoiu GC, Abood ME, Brailoiu E, Patel S (2014) Two-pore channels provide insight into the evolution of voltage-gated Ca2+ and Na+ channels. Sci Signal 7:ra109. https://doi.org/10.1126/scisignal.2005450
Ruas M, Davis LC, Chen CC, Morgan AJ, Chuang KT, Walseth TF, Grimm C, Garnham C, Powell T, Platt N, Platt FM, Biel M, Wahl-Schott C, Parrington J, Galione A (2015) Expression of Ca(2)(+)-permeable two-pore channels rescues NAADP signalling in TPC-deficient cells. EMBO J 34:1743–1758. https://doi.org/10.15252/embj.201490009
Rybalchenko V, Ahuja M, Coblentz J, Churamani D, Patel S, Kiselyov K, Muallem S (2012) Membrane potential regulates nicotinic acid adenine dinucleotide phosphate (NAADP) dependence of the pH- and Ca2+−sensitive organellar two-pore channel TPC1. J Biol Chem 287:20407–20416. https://doi.org/10.1074/jbc.M112.359612
Sakurai Y, Kolokoltsov AA, Chen CC, Tidwell MW, Bauta WE, Klugbauer N, Grimm C, Wahl-Schott C, Biel M, Davey RA (2015) Ebola virus. Two-pore channels control Ebola virus host cell entry and are drug targets for disease treatment. Science 347:995–998. https://doi.org/10.1126/science.1258758
Schulze C, Sticht H, Meyerhoff P, Dietrich P (2011) Differential contribution of EF-hands to the Ca(2)(+)-dependent activation in the plant two-pore channel TPC1. Plant J 68:424–432. https://doi.org/10.1111/j.1365-313X.2011.04697.x
She J, Guo J, Chen Q, Zeng W, Jiang Y, Bai XC (2018) Structural insights into the voltage and phospholipid activation of the mammalian TPC1 channel. Nature 556:130–134. https://doi.org/10.1038/nature26139
She J, Zeng W, Guo J, Chen Q, Bai XC, Jiang Y (2019) Structural mechanisms of phospholipid activation of the human TPC2 channel. eLife 8. https://doi.org/10.7554/eLife.45222
Sulem P, Gudbjartsson DF, Stacey SN, Helgason A, Rafnar T, Jakobsdottir M, Steinberg S, Gudjonsson SA, Palsson A, Thorleifsson G, Palsson S, Sigurgeirsson B, Thorisdottir K, Ragnarsson R, Benediktsdottir KR, Aben KK, Vermeulen SH, Goldstein AM, Tucker MA, Kiemeney LA, Olafsson JH, Gulcher J, Kong A, Thorsteinsdottir U, Stefansson K (2008) Two newly identified genetic determinants of pigmentation in Europeans. Nat Genet 40:835–837. https://doi.org/10.1038/ng.160
Tao X, Lee A, Limapichat W, Dougherty DA, MacKinnon R (2010) A gating charge transfer center in voltage sensors. Science 328:67–73. https://doi.org/10.1126/science.1185954
Vieira-Pires RS, Morais-Cabral JH (2010) 3(10) helices in channels and other membrane proteins. J Gen Physiol 136:585–592. https://doi.org/10.1085/jgp.201010508
Wang X, Zhang X, Dong XP, Samie M, Li X, Cheng X, Goschka A, Shen D, Zhou Y, Harlow J, Zhu MX, Clapham DE, Ren D, Xu H (2012) TPC proteins are phosphoinositide- activated sodium-selective ion channels in endosomes and lysosomes. Cell 151:372–383. https://doi.org/10.1016/j.cell.2012.08.036
Wu J, Yan Z, Li Z, Yan C, Lu S, Dong M, Yan N (2015) Structure of the voltage-gated calcium channel Cav1.1 complex. Science 350:aad2395. https://doi.org/10.1126/science.aad2395
Xu H, Ren D (2015) Lysosomal physiology. Annu Rev Physiol 77:57–80. https://doi.org/10.1146/annurev-physiol-021014-071649
Yu FH, Catterall WA (2004) The VGL-chanome: a protein superfamily specialized for electrical signaling and ionic homeostasis. Sci STKE 2004:re15. https://doi.org/10.1126/stke.2532004re15
Zong X, Schieder M, Cuny H, Fenske S, Gruner C, Rotzer K, Griesbeck O, Harz H, Biel M, Wahl-Schott C (2009) The two-pore channel TPCN2 mediates NAADP-dependent Ca(2+)-release from lysosomal stores. Pflugers Arch 458:891–899. https://doi.org/10.1007/s00424-009-0690-y
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2022 Springer Nature Switzerland AG
About this chapter
Cite this chapter
She, J., Guo, J., Jiang, Y. (2022). Structure and Function of Plant and Mammalian TPC Channels. In: Wahl-Schott, C., Biel, M. (eds) Endolysosomal Voltage-Dependent Cation Channels. Handbook of Experimental Pharmacology, vol 278. Springer, Cham. https://doi.org/10.1007/164_2022_599
Download citation
DOI: https://doi.org/10.1007/164_2022_599
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-31522-0
Online ISBN: 978-3-031-31523-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)