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NAADP-Dependent TPC Current

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Endolysosomal Voltage-Dependent Cation Channels

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 278))

Abstract

Two-pore channels, TPC1 and TPC2, are Ca2+- and Na+-permeable cation channels expressed on the membranes of endosomes and lysosomes in nearly all mammalian cells. These channels have been implicated in Ca2+ signaling initiated from the endolysosomes, vesicular trafficking, cellular metabolism, macropinocytosis, and viral infection. Although TPCs have been shown to mediate Ca2+ release from acidic organelles in response to NAADP (nicotinic acid adenine dinucleotide phosphate), the most potent Ca2+ mobilizing messenger, questions remain whether NAADP is a direct ligand of these channels. In whole-endolysosomal patch clamp recordings, it has been difficult to detect NAADP-evoked currents in vacuoles that expressed TPC1 or TPC2, while PI(3,5)P2 (phosphatidylinositol 3,5-bisphosphate) activated a highly Na+-selective current under the same experimental configuration. In this chapter, we summarize recent progress in this area and provide our observations on NAADP-elicited TPC2 currents from enlarged endolysosomes as well as their possible relationships with the currents evoked by PI(3,5)P2. We propose that TPCs are channels dually regulated by PI(3,5)P2 and NAADP in an interdependent manner and the two endogenous ligands may have both distinguished and cooperative roles.

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References

  • Aarhus R, Dickey DM, Graeff RM, Gee KR, Walseth TF, Lee HC (1996) Activation and inactivation of Ca2+ release by NAADP+. J Biol Chem 271:8513–8516

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arredouani A, Ruas M, Collins SC, Parkesh R, Clough F, Pillinger T, Coltart G, Rietdorf K, Royle A, Johnson P et al (2015) Nicotinic acid adenine dinucleotide phosphate (NAADP) and endolysosomal two-pore channels modulate membrane excitability and stimulus-secretion coupling in mouse pancreatic β cells. J Biol Chem 290:21376–21392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bak J, Billington RA, Timar G, Dutton AC, Genazzani AA (2001) NAADP receptors are present and functional in the heart. Curr Biol 11:987–990

    Article  CAS  PubMed  Google Scholar 

  • Billington RA, Genazzani AA (2000) Characterization of NAADP+ binding in sea urchin eggs. Biochem Biophys Res Commun 276:112–116

    Article  CAS  PubMed  Google Scholar 

  • Bonangelino CJ, Nau JJ, Duex JE, Brinkman M, Wurmser AE, Gary JD, Emr SD, Weisman LS (2002) Osmotic stress-induced increase of phosphatidylinositol 3,5-bisphosphate requires Vac14p, an activator of the lipid kinase Fab1p. J Cell Biol 156:1015–1028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brailoiu E, Churamani D, Pandey V, Brailoiu GC, Tuluc F, Patel S, Dun NJ (2006) Messenger-specific role for nicotinic acid adenine dinucleotide phosphate in neuronal differentiation. J Biol Chem 281:15923–15928

    Article  CAS  PubMed  Google Scholar 

  • Brailoiu E, Churamani D, Cai X, Schrlau MG, Brailoiu GC, Gao X, Hooper R, Boulware MJ, Dun NJ, Marchant JS et al (2009) Essential requirement for two-pore channel 1 in NAADP-mediated calcium signaling. J Cell Biol 186:201–209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Brailoiu E, Rahman T, Churamani D, Prole DL, Brailoiu GC, Hooper R, Taylor CW, Patel S (2010) An NAADP-gated two-pore channel targeted to the plasma membrane uncouples triggering from amplifying Ca2+ signals. J Biol Chem 285:38511–38516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Calcraft PJ, Ruas M, Pan Z, Cheng X, Arredouani A, Hao X, Tang J, Rietdorf K, Teboul L, Chuang KT et al (2009) NAADP mobilizes calcium from acidic organelles through two-pore channels. Nature 459:596–600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cancela JM, Churchill GC, Galione A (1999) Coordination of agonist-induced Ca2+-signalling patterns by NAADP in pancreatic acinar cells. Nature 398:74–76

    Article  CAS  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen CC, Cang C, Fenske S, Butz E, Chao YK, Biel M, Ren D, Wahl-Schott C, Grimm C (2017) Patch-clamp technique to characterize ion channels in enlarged individual endolysosomes. Nat Protoc 12:1639–1658

    Article  CAS  PubMed  Google Scholar 

  • Chini EN, Beers KW, Dousa TP (1995) Nicotinate adenine dinucleotide phosphate (NAADP) triggers a specific calcium release system in sea urchin eggs. J Biol Chem 270:3216–3223

    Article  CAS  PubMed  Google Scholar 

  • Churchill GC, Okada Y, Thomas JM, Genazzani AA, Patel S, Galione A (2002) NAADP mobilizes Ca2+ from reserve granules, lysosome-related organelles, in sea urchin eggs. Cell 111:703–708

    Article  CAS  PubMed  Google Scholar 

  • Dickinson GD, Patel S (2003) Modulation of NAADP (nicotinic acid-adenine dinucleotide phosphate) receptors by K+ ions: evidence for multiple NAADP receptor conformations. Biochem J 375:805–812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dong XP, Cheng X, Mills E, Delling M, Wang F, Kurz T, Xu H (2008) The type IV mucolipidosis-associated protein TRPML1 is an endolysosomal iron release channel. Nature 455:992–996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dong XP, Shen D, Wang X, Dawson T, Li X, Zhang Q, Cheng X, Zhang Y, Weisman LS, Delling M et al (2010) PI(3,5)P2 controls membrane trafficking by direct activation of mucolipin Ca2+ release channels in the endolysosome. Nat Commun 1:38

    Article  PubMed  Google Scholar 

  • Dove SK, Cooke FT, Douglas MR, Sayers LG, Parker PJ, Michell RH (1997) Osmotic stress activates phosphatidylinositol-3,5-bisphosphate synthesis. Nature 390:187–192

    Article  CAS  PubMed  Google Scholar 

  • Du C, Guan X, Yan J (2022) Two-pore channel blockade by phosphoinositide kinase inhibitors YM201636 and PI-103 determined by a histidine residue near pore-entrance. bioRxiv:480111. https://doi.org/10.1101/2022.02.11.480111

  • Favia A, Desideri M, Gambara G, D'Alessio A, Ruas M, Esposito B, Del Bufalo D, Parrington J, Ziparo E, Palombi F et al (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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Freeman SA, Uderhardt S, Saric A, Collins RF, Buckley CM, Mylvaganam S, Boroumand P, Plumb J, Germain RN, Ren D, Grinstein S (2020) Lipid-gated monovalent ion fluxes regulate endocytic traffic and support immune surveillance. Science 367:301–305

    Article  CAS  PubMed  Google Scholar 

  • Gary JD, Wurmser AE, Bonangelino CJ, Weisman LS, Emr SD (1998) Fab1p is essential for PtdIns(3)P 5-kinase activity and the maintenance of vacuolar size and membrane homeostasis. J Cell Biol 143:65–79

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Genazzani AA, Empson RM, Galione A (1996) Unique inactivation properties of NAADP-sensitive Ca2+ release. J Biol Chem 271:11599–11602

    Article  CAS  PubMed  Google Scholar 

  • Gerndt S, Chen CC, Chao YK, Yuan Y, Burgstaller S, Scotto Rosato A, Krogsaeter E, Urban N, Jacob K, Nguyen ONP et al (2020) Agonist-mediated switching of ion selectivity in TPC2 differentially promotes lysosomal function. Elife 9:e54712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grimm C, Holdt LM, Chen CC, Hassan S, Müller C, Jörs S, Cuny H, Kissing S, Schröder B, Butz E et al (2014) High susceptibility to fatty liver disease in two-pore channel 2-deficient mice. Nat Commun 5:4699

    Article  CAS  PubMed  Google Scholar 

  • Grimm C, Chen CC, Wahl-Schott C, Biel M (2017) Two-pore channels: catalyzers of endolysosomal transport and function. Front Pharmacol 8:45

    Article  PubMed  PubMed Central  Google Scholar 

  • Gunaratne GS, Yang Y, Li F, Walseth TF, Marchant JS (2018) NAADP-dependent Ca2+ signaling regulates middle east respiratory syndrome-coronavirus pseudovirus translocation through the endolysosomal system. Cell Calcium 75:30–41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gunaratne GS, Su P, Marchant JS, Slama JT, Walseth TF (2019) 5-Azido-8-ethynyl-NAADP: a bifunctional, clickable photoaffinity probe for the identification of NAADP receptors. Biochim Biophys Acta Mol Cell Res 1866:1180–1188

    Article  CAS  PubMed  Google Scholar 

  • Gunaratne GS, Brailoiu E, He S, Unterwald EM, Patel S, Slama JT, Walseth TF, Marchant JS (2021) Essential requirement for JPT2 in NAADP-evoked Ca2+ signaling. Sci Signal 14:eabd5605

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guse AH, Diercks BP (2018) Integration of nicotinic acid adenine dinucleotide phosphate (NAADP)-dependent calcium signalling. J Physiol 596:2735–2743

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ikonomov OC, Sbrissa D, Mlak K, Kanzaki M, Pessin J, Shisheva A (2002) Functional dissection of lipid and protein kinase signals of PIKfyve reveals the role of PtdIns 3,5-P2 production for endomembrane integrity. J Biol Chem 277:9206–9211

    Article  CAS  PubMed  Google Scholar 

  • Jefferies HB, Cooke FT, Jat P, Boucheron C, Koizumi T, Hayakawa M, Kaizawa H, Ohishi T, Workman P, Waterfield MD et al (2008) A selective PIKfyve inhibitor blocks PtdIns(3,5)P2 production and disrupts endomembrane transport and retroviral budding. EMBO Rep 9:164–170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jha A, Ahuja M, Patel S, Brailoiu E, Muallem S (2014) Convergent regulation of the lysosomal two-pore channel-2 by Mg2+, NAADP, PI(3,5)P2 and multiple protein kinases. EMBO J 33:501–511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kinnear NP, Boittin FX, Thomas JM, Galione A, Evans AM (2004) Lysosome-sarcoplasmic reticulum junctions. A trigger zone for calcium signaling by nicotinic acid adenine dinucleotide phosphate and endothelin-1. J Biol Chem 279:54319–54326

    Article  CAS  PubMed  Google Scholar 

  • Krogsaeter E, Tang R, Grimm C (2021) JPT2: the missing link between intracellular Ca2+ release channels and NAADP? Cell Calcium 97:102405

    Article  CAS  PubMed  Google Scholar 

  • Kuma A, Hatano M, Matsui M, Yamamoto A, Nakaya H, Yoshimori T, Ohsumi Y, Tokuhisa T, Mizushima N (2004) The role of autophagy during the early neonatal starvation period. Nature 432:1032–1036

    Article  CAS  PubMed  Google Scholar 

  • Lear PV, González-Touceda D, Porteiro Couto B, Viaño P, Guymer V, Remzova E, Tunn R, Chalasani A, García-Caballero T, Hargreaves IP et al (2015) Absence of intracellular ion channels TPC1 and TPC2 leads to mature-onset obesity in male mice, due to impaired lipid availability for thermogenesis in brown adipose tissue. Endocrinology 156:975–986

    Article  CAS  PubMed  Google Scholar 

  • Lee HC, Aarhus R (1995) A derivative of NADP mobilizes calcium stores insensitive to inositol trisphosphate and cyclic ADP-ribose. J Biol Chem 270:2152–2157

    Article  CAS  PubMed  Google Scholar 

  • Lee HC, Aarhus R, Gee KR, Kestner T (1997) Caged nicotinic acid adenine dinucleotide phosphate. Synthesis and use. J Biol Chem 272:4172–4178

    Article  CAS  PubMed  Google Scholar 

  • Lin-Moshier Y, Walseth TF, Churamani D, Davidson SM, Slama JT, Hooper R, Brailoiu E, Patel S, Marchant JS (2012) Photoaffinity labeling of nicotinic acid adenine dinucleotide phosphate (NAADP) targets in mammalian cells. J Biol Chem 287:2296–2307

    Article  CAS  PubMed  Google Scholar 

  • Macgregor A, Yamasaki M, Rakovic S, Sanders L, Parkesh R, Churchill GC, Galione A, Terrar DA (2007) NAADP controls cross-talk between distinct Ca2+ stores in the heart. J Biol Chem 282:15302–15311

    Article  CAS  PubMed  Google Scholar 

  • Marchant JS, Patel S (2013) Questioning regulation of two-pore channels by NAADP. Messenger (Los Angel) 2:113–119

    PubMed  Google Scholar 

  • Marchant JS, Lin-Moshier Y, Walseth TF, Patel S (2012) The molecular basis for Ca2+ signalling by NAADP: two-pore channels in a complex? Messenger (Los Angel) 1:63–76

    PubMed  Google Scholar 

  • Medina DL, Ballabio A (2015) Lysosomal calcium regulates autophagy. Autophagy 11:970–971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Medina DL, Di Paola S, Peluso I, Armani A, De Stefani D, Venditti R, Montefusco S, Scotto-Rosato A, Prezioso C, Forrester A et al (2015) Lysosomal calcium signalling regulates autophagy through calcineurin and TFEB. Nat Cell Biol 17:288–299

    Article  PubMed  PubMed Central  Google Scholar 

  • Morgan AJ, Galione A (2014) Two-pore channels (TPCs): current controversies. Bioessays 36:173–183

    Article  CAS  PubMed  Google Scholar 

  • Nakada-Tsukui K, Watanabe N, Maehama T, Nozaki T (2019) Phosphatidylinositol kinases and phosphatases in Entamoeba histolytica. Front Cell Infect Microbiol 9:150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nguyen ON, Grimm C, Schneider LS, Chao YK, Atzberger C, Bartel K, Watermann A, Ulrich M, Mayr D, Wahl-Schott C et al (2017) Two-pore channel function is crucial for the migration of invasive cancer cells. Cancer Res 77:1427–1438

    Article  CAS  PubMed  Google Scholar 

  • Ogunbayo OA, Zhu Y, Rossi D, Sorrentino V, Ma J, Zhu MX, Evans AM (2011) Cyclic adenosine diphosphate ribose activates ryanodine receptors, whereas NAADP activates two-pore domain channels. J Biol Chem 286:9136–9140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ogunbayo OA, Duan J, Xiong J, Wang Q, Feng X, Ma J, Zhu MX, Evans AM (2018) mTORC1 controls lysosomal Ca2+ release through the two-pore channel TPC2. Sci Signal 11:eaao5775

    Article  PubMed  PubMed Central  Google Scholar 

  • Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, Guo L, Guo R, Chen T, Hu J et al (2020) Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun 11:1620

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patel S, Churchill GC, Galione A (2000a) Unique kinetics of nicotinic acid-adenine dinucleotide phosphate (NAADP) binding enhance the sensitivity of NAADP receptors for their ligand. Biochem J 352:725–729

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patel S, Churchill GC, Sharp T, Galione A (2000b) Widespread distribution of binding sites for the novel Ca2+-mobilizing messenger, nicotinic acid adenine dinucleotide phosphate, in the brain. J Biol Chem 275:36495–36497

    Article  CAS  PubMed  Google Scholar 

  • Patel S, Churamani D, Brailoiu E (2017) NAADP-evoked Ca2+ signals through two-pore channel-1 require arginine residues in the first S4-S5 linker. Cell Calcium 68:1–4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pitt SJ, Funnell TM, Sitsapesan M, Venturi E, Rietdorf K, Ruas M, Ganesan A, Gosain R, Churchill GC, Zhu MX et al (2010) TPC2 is a novel NAADP-sensitive Ca2+ release channel, operating as a dual sensor of luminal pH and Ca2+. J Biol Chem 285:35039–35046

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pitt SJ, Lam AK, 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

    Article  PubMed  PubMed Central  Google Scholar 

  • Pitt SJ, Reilly-O'Donnell B, Sitsapesan R (2016) Exploring the biophysical evidence that mammalian two-pore channels are NAADP-activated calcium-permeable channels. J Physiol 594:4171–4179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rah S-Y, Lee Y-H, Kim U-H (2017) NAADP-mediated Ca2+ signaling promotes autophagy and protects against LPS-induced liver injury. FASEB J 31:3126–3137

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Roggenkamp HG, Khansahib I, Hernandez LC, Zhang Y, Lodygin D, Krüger A, Gu F, Möckl F, Löhndorf A, Wolters V et al (2021) HN1L/JPT2: a signaling protein that connects NAADP generation to Ca2+ microdomain formation. Sci Signal 14:eabd5647

    Article  CAS  PubMed  Google Scholar 

  • Ruas M, Rietdorf K, Arredouani A, Davis LC, Lloyd-Evans E, Koegel H, Funnell TM, Morgan AJ, Ward JA, Watanabe K et al (2010) Purified TPC isoforms form NAADP receptors with distinct roles for Ca2+ signaling and endolysosomal trafficking. Curr Biol 20:703–709

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ruas M, Davis LC, Chen C-C, Morgan AJ, Chuang K-T, Walseth TF, Grimm C, Garnham C, Powell T, Platt N et al (2015a) Expression of Ca2+-permeable two-pore channels rescues NAADP signalling in TPC-deficient cells. EMBO J 34:1743–1758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ruas M, Galione A, Parrington J (2015b) Two-pore channels: lessons from mutant mouse models. Messenger (Los Angel) 4:4–22

    PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schieder M, Rotzer K, Bruggemann A, Biel M, Wahl-Schott C (2010a) Planar patch clamp approach to characterize ionic currents from intact lysosomes. Sci Signal 3:pl3

    Article  CAS  PubMed  Google Scholar 

  • Schieder M, Rotzer K, Bruggemann A, Biel M, Wahl-Schott CA (2010b) Characterization of two-pore channel 2 (TPCN2)-mediated Ca2+ currents in isolated lysosomes. J Biol Chem 285:21219–21222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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:e45222

    Article  PubMed  PubMed Central  Google Scholar 

  • Shen D, Wang X, Xu H (2011) Pairing Phosphoinositides with calcium ions in Endolysosomal dynamics: phosphoinositides controls the direction and specificity of membrane trafficking by regulating the activity of calcium channels in the endolysosomes. Bioessays 33:448–457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stokłosa P, Probst D, Reymond JL, Peinelt C (2020) The name tells the story: two-pore channels. Cell Calcium 89:102215

    Article  PubMed  Google Scholar 

  • Takatori S, Tatematsu T, Cheng J, Matsumoto J, Akano T, Fujimoto T (2016) Phosphatidylinositol 3,5-bisphosphate-rich membrane domains in endosomes and lysosomes. Traffic 17:154–167

    Article  CAS  PubMed  Google Scholar 

  • Volpicelli-Daley L, De Camilli P (2007) Phosphoinositides' link to neurodegeneration. Nat Med 13:784–786

    Article  CAS  PubMed  Google Scholar 

  • Walseth TF, Lin-Moshier Y, Weber K, Marchant JS, Slama JT, Guse AH (2012a) Nicotinic acid adenine dinucleotide 2'-phosphate (NAADP) binding proteins in T-lymphocytes. Messenger (Los Angel) 1:86–94

    PubMed  Google Scholar 

  • Walseth TF, Lin-Moshier Y, Jain P, Ruas M, Parrington J, Galione A, Marchant JS, Slama JT (2012b) Photoaffinity Labeling of high affinity nicotinic acid adenine dinucleotide phosphate (NAADP)-binding proteins in sea urchin egg. J Biol Chem 287:2308–2315

    Article  CAS  PubMed  Google Scholar 

  • Wang X, Zhang X, Dong XP, Samie M, Li X, Cheng X, Goschka A, Shen D, Zhou Y, Harlow J et al (2012) TPC proteins are phosphoinositide- activated sodium-selective ion channels in endosomes and lysosomes. Cell 151:372–383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamaguchi S, Jha A, Li Q, Soyombo AA, Dickinson GD, Churamani D, Brailoiu E, Patel S, Muallem S (2011) Transient receptor potential mucolipin 1 (TRPML1) and two-pore channels are functionally independent organellar ion channels. J Biol Chem 286:22934–22942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamasaki M, Masgrau R, Morgan AJ, Churchill GC, Patel S, Ashcroft SJ, Galione A (2004) Organelle selection determines agonist-specific Ca2+ signals in pancreatic acinar and beta cells. J Biol Chem 279:7234–7240

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Guan X, Shah K, Yan J (2021) Lsm12 is an NAADP receptor and a two-pore channel regulatory protein required for calcium mobilization from acidic organelles. Nat Commun 12:4739

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao Z, Qin P, Huang YW (2021) Lysosomal ion channels involved in cellular entry and uncoating of enveloped viruses: implications for therapeutic strategies against SARS-CoV-2. Cell Calcium 94:102360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu MX, Ma J, Parrington J, Galione A, Evans AM (2010) TPCs: endolysosomal channels for Ca2+ mobilization from acidic organelles triggered by NAADP. FEBS Lett 584:1966–1974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zolov SN, Bridges D, Zhang Y, Lee W-W, Riehle E, Verma R, Lenk GM, Converso-Baran K, Weide T, Albin RL et al (2012) In vivo, Pikfyve generates PI(3,5)P2, which serves as both a signaling lipid and the major precursor for PI5P. Proc Natl Acad Sci U S A 109:17472–17477

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 Ca2+-release from lysosomal stores. Pflugers Arch 458:891–899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported in part by US National Institutes of Health grant R01 NS102452 (to MXZ) and National Natural Science Foundation of China grant 92054102 (to QW). QW is a recipient of American Heart Association Postdoctoral Fellowship 17POST33661282.

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Authors and Affiliations

  1. Beijing Children’s Hospital, Capital Medical University, Beijing, China

    Qiaochu Wang

  2. Department of Integrative Biology and Pharmacology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA

    Qiaochu Wang & Michael X. Zhu

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  1. Qiaochu Wang
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  2. Michael X. Zhu
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Correspondence to Michael X. Zhu .

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  1. Institute for Cardiovascular Physiology and Pathophysiology, LMU, Planegg-Martinsried, Germany

    Christian Wahl-Schott

  2. Department Pharmazie der LMU, Pharmakologie für Naturwissenschaften, München, Germany

    Martin Biel

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Wang, Q., Zhu, M.X. (2022). NAADP-Dependent TPC Current. 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_606

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