Abstract
Bacterial and eukaryotic polyphosphate (polyP) accumulates in acidic vacuoles that have been named the acidocalcisomes to highlight their high calcium content together with the presence of other inorganic and organic cations. The large amount of polyP and cations in acidocalcisomes explains their high electron density when they are examined by electron microscopy. PolyP synthesis and translocation to the yeast acidocalcisome-like vacuole is catalyzed by the vacuolar transporter chaperone 4 (Vtc4), which is the catalytic subunit of the VTC complex and requires a proton gradient generated by the proton pump for this translocation. Similar VTC complexes have been found in acidocalcisomes of trypanosomatids and algae. Acidocalcisome polyP could be rapidly hydrolyzed under alkaline or hyposmotic stress. Hydrolysis of acidocalcisome polyP has been studied in trypanosomatids where it is catalyzed by an exopolyphosphatase (PPX) or by the exopolyphosphatase activity of a vacuolar soluble pyrophosphatase (VSP). It has been found that this hydrolytic process favors the release of osmolytes (phosphorus and cations) to the cytosol helping the regulatory volume decrease that follows hyposmotic stress. In some mammalian cells, like platelets and mast cells, acidocalcisome polyP is released into the circulation where it can have potent procoagulant, antifibrinolytic, and inflammatory actions and, under pathological conditions, could be involved in thrombosis. Fusion of acidocalcisomes with the contractile vacuole complex of Chlamydomonas reinhardtii, Dictyostelium discoideum, and Trypanosoma cruzi could also be involved in transfer of polyP or its hydrolytic products to the bladder to increase its osmolarity and ensuing water uptake necessary for its function. Finally, downregulation and upregulation of the expression of enzymes involved in polyP metabolism have revealed the role of polyP in growth, infectivity, and persistence of different parasites.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Aksoy M, Pootakham W, Grossman AR (2014) Critical function of a Chlamydomonas reinhardtii putative polyphosphate polymerase subunit during nutrient deprivation. Plant Cell 26(10):4214–4229. doi:10.1105/tpc.114.129270
Besteiro S, Tonn D, Tetley L et al (2008) The AP3 adaptor is involved in the transport of membrane proteins to acidocalcisomes of Leishmania. J Cell Sci 121(Pt 5):561–570
de Jesus TC, Tonelli RR, Nardelli SC et al (2010) Target of rapamycin (TOR)-like 1 kinase is involved in the control of polyphosphate levels and acidocalcisome maintenance in Trypanosoma brucei. J Biol Chem 285(31):24131–24140. doi:10.1074/jbc.M110.120212
Docampo R (2014) Polyphosphate: a target for thrombosis attenuation. Blood 124(22):3177–3178. doi:10.1182/blood-2014-09-601641
Docampo R, Moreno SN (2011) Acidocalcisomes. Cell Calcium 50(2):113–119. doi:10.1016/j.ceca.2011.05.012
Docampo R, Scott DA, Vercesi AE et al (1995) Intracellular Ca2+ storage in acidocalcisomes of Trypanosoma cruzi. Biochem J 310(Pt 3):1005–1012
Docampo R, de Souza W, Miranda K et al (2005) Acidocalcisomes – conserved from bacteria to man. Nat Rev Microbiol 3(3):251–261. doi:10.1038/nrmicro1097
Docampo R, Jimenez V, Lander N et al (2013) New insights into roles of acidocalcisomes and contractile vacuole complex in osmoregulation in protists. Int Rev Cell Mol Biol 305:69–113. doi:10.1016/B978-0-12-407695-2.00002-0
Espiau B, Lemercier G, Ambit A et al (2006) A soluble pyrophosphatase, a key enzyme for polyphosphate metabolism in Leishmania. J Biol Chem 281(3):1516–1523. doi:10.1074/jbc.M506947200
Fang J, Rohloff P, Miranda K et al (2007a) Ablation of a small transmembrane protein of Trypanosoma brucei (TbVTC1) involved in the synthesis of polyphosphate alters acidocalcisome biogenesis and function, and leads to a cytokinesis defect. Biochem J 407(2):161–170
Fang J, Ruiz FA, Docampo M et al (2007b) Overexpression of a Zn2+-sensitive soluble exopolyphosphatase from Trypanosoma cruzi depletes polyphosphate and affects osmoregulation. J Biol Chem 282(44):32501–32510. doi:10.1074/jbc.M704841200
Galizzi M, Bustamante JM, Fang J et al (2013) Evidence for the role of vacuolar soluble pyrophosphatase and inorganic polyphosphate in Trypanosoma cruzi persistence. Mol Microbiol 90(4):699–715. doi:10.1111/mmi.12392
Gerasimaite R, Sharma S, Desfougeres Y et al (2014) Coupled synthesis and translocation restrains polyphosphate to acidocalcisome-like vacuoles and prevents its toxicity. J Cell Sci 127(23):5093–5104. doi:10.1242/jcs.159772
Ghosh S, Shukla D, Suman K et al (2013) Inositol hexakisphosphate kinase 1 maintains hemostasis in mice by regulating platelet polyphosphate levels. Blood 122(8):1478–1486. doi:10.1182/blood-2013-01-481549
Gomez-Garcia MR, Kornberg A (2004) Formation of an actin-like filament concurrent with the enzymatic synthesis of inorganic polyphosphate. Proc Natl Acad Sci U S A 101(45):15876–15880. doi:10.1073/pnas.0406923101
Hong-Hermesdorf A, Miethke M, Gallaher SD et al (2014) Subcellular metal imaging identifies dynamic sites of Cu accumulation in Chlamydomonas. Nat Chem Biol 10(12):1034–1042. doi:10.1038/nchembio.1662
Hothorn M, Neumann H, Lenherr ED et al (2009) Catalytic core of a membrane-associated eukaryotic polyphosphate polymerase. Science 324(5926):513–516. doi:10.1126/science.1168120
Huang G, Bartlett PJ, Thomas AP et al (2013) Acidocalcisomes of Trypanosoma brucei have an inositol 1,4,5-trisphosphate receptor that is required for growth and infectivity. Proc Natl Acad Sci U S A 110(5):1887–1892. doi:10.1073/pnas.1216955110
Huang G, Ulrich PN, Storey M et al (2014) Proteomic analysis of the acidocalcisome, an organelle conserved from bacteria to human cells. PLoS Pathog 10(12):e1004555. doi:10.1371/journal.ppat.1004555
Jimenez V, Docampo R (2015) TcPho91 is a contractile vacuole phosphate sodium symporter that regulates phosphate and polyphosphate metabolism in Trypanosoma cruzi. Mol Microbiol 97(5):911–925. doi:10.1111/mmi.13075
Kotsikorou E, Song Y, Chan JM et al (2005) Bisphosphonate inhibition of the exopolyphosphatase activity of the Trypanosoma brucei soluble vacuolar pyrophosphatase. J Med Chem 48(19):6128–6139. doi:10.1021/jm058220g
Lander N, Ulrich PN, Docampo R (2013) Trypanosoma brucei vacuolar transporter chaperone 4 (TbVtc4) is an acidocalcisome polyphosphate kinase required for in vivo infection. J Biol Chem 288(47):34205–34216. doi:10.1074/jbc.M113.518993
Lemercier G, Espiau B, Ruiz FA et al (2004) A pyrophosphatase regulating polyphosphate metabolism in acidocalcisomes is essential for Trypanosoma brucei virulence in mice. J Biol Chem 279(5):3420–3425. doi:10.1074/jbc.M309974200
Li FJ, He CY (2014) Acidocalcisome is required for autophagy in Trypanosoma brucei. Autophagy 10(11):1978–1988. doi:10.4161/auto.36183
Li ZH, Alvarez VE, De Gaudenzi JG et al (2011) Hyperosmotic stress induces aquaporin-dependent cell shrinkage, polyphosphate synthesis, amino acid accumulation, and global gene expression changes in Trypanosoma cruzi. J Biol Chem 286(51):43959–43971. doi:10.1074/jbc.M111.311530
Livermore TM, Chubb JR, Saiardi A (2016) Developmental accumulation of inorganic polyphosphate affects germination and energetic metabolism in Dictyostelium discoideum. Proc Natl Acad Sci U S A 113(4):996–1001. doi:10.1073/pnas.1519440113
Lonetti A, Szijgyarto Z, Bosch D et al (2011) Identification of an evolutionarily conserved family of inorganic polyphosphate endopolyphosphatases. J Biol Chem 286(37):31966–31974. doi:10.1074/jbc.M111.266320
Lu HG, Zhong L, de Souza W et al (1998) Ca2+ content and expression of an acidocalcisomal calcium pump are elevated in intracellular forms of Trypanosoma cruzi. Mol Cell Biol 18(4):2309–2323
Luo S, Vieira M, Graves J et al (2001) A plasma membrane-type Ca2+-ATPase co-localizes with a vacuolar H+-pyrophosphatase to acidocalcisomes of Toxoplasma gondii. Embo J 20(1–2):55–64. doi:10.1093/emboj/20.1.55
Luo S, Rohloff P, Cox J et al (2004) Trypanosoma brucei plasma membrane-type Ca2+-ATPase 1 (TbPMC1) and 2 (TbPMC2) genes encode functional Ca2+-ATPases localized to the acidocalcisomes and plasma membrane, and essential for Ca2+ homeostasis and growth. J Biol Chem 279(14):14427–14439. doi:10.1074/jbc.M309978200
Luo S, Ruiz FA, Moreno SN (2005) The acidocalcisome Ca2+-ATPase (TgA1) of Toxoplasma gondii is required for polyphosphate storage, intracellular calcium homeostasis and virulence. Mol Microbiol 55(4):1034–1045. doi:10.1111/j.1365-2958.2004.04464.x
Madeira da Silva L, Beverley SM (2010) Expansion of the target of rapamycin (TOR) kinase family and function in Leishmania shows that TOR3 is required for acidocalcisome biogenesis and animal infectivity. Proc Natl Acad Sci U S A 107(26):11965–11970. doi:10.1073/pnas.1004599107
Marchesini N, Ruiz FA, Vieira M et al (2002) Acidocalcisomes are functionally linked to the contractile vacuole of Dictyostelium discoideum. J Biol Chem 277(10):8146–8153. doi:10.1074/jbc.M111130200
Mendoza M, Mijares A, Rojas H et al (2002) Physiological and morphological evidences for the presence acidocalcisomes in Trypanosoma evansi: single cell fluorescence and 31P NMR studies. Mol Biochem Parasitol 125(1–2):23–33
Miranda K, Benchimol M, Docampo R et al (2000) The fine structure of acidocalcisomes in Trypanosoma cruzi. Parasitol Res 86(5):373–384
Miranda K, Docampo R, Grillo O et al (2004a) Dynamics of polymorphism of acidocalcisomes in Leishmania parasites. Histochem Cell Biol 121(5):407–418. doi:10.1007/s00418-004-0646-4
Miranda K, Rodrigues CO, Hentchel J et al (2004b) Acidocalcisomes of Phytomonas francai possess distinct morphological characteristics and contain iron. Microsc Microanal 10(5):647–655. doi:10.1017/S1431927604040887
Miranda K, Docampo R, Grillo O et al (2004c) Acidocalcisomes of trypanosomatids have species-specific elemental composition. Protist 155(4):395–405. doi:10.1078/1434461042650361
Montalvetti A, Rohloff P, Docampo R (2004) A functional aquaporin co-localizes with the vacuolar proton pyrophosphatase to acidocalcisomes and the contractile vacuole complex of Trypanosoma cruzi. J Biol Chem 279(37):38673–38682. doi:10.1074/jbc.M406304200
Moreno SN, Zhong L (1996) Acidocalcisomes in Toxoplasma gondii tachyzoites. Biochem J 313(Pt 2):655–659
Moreno B, Urbina JA, Oldfield E et al (2000) 31P NMR spectroscopy of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major. Evidence for high levels of condensed inorganic phosphates. J Biol Chem 275(37):28356–28362. doi:10.1074/jbc.M003893200
Moreno B, Rodrigues CO, Bailey BN et al (2002) Magic-angle spinning 31P NMR spectroscopy of condensed phosphates in parasitic protozoa: visualizing the invisible. FEBS Lett 523(1–3):207–212
Moreno-Sanchez D, Hernandez-Ruiz L, Ruiz FA et al (2012) Polyphosphate is a novel pro-inflammatory regulator of mast cells and is located in acidocalcisomes. J Biol Chem 287(34):28435–28444. doi:10.1074/jbc.M112.385823
Morrissey JH, Choi SH, Smith SA (2012) Polyphosphate: an ancient molecule that links platelets, coagulation, and inflammation. Blood 119(25):5972–5979. doi:10.1182/blood-2012-03-306605
Motta LS, Ramos IB, Gomes FM et al (2009) Proton-pyrophosphatase and polyphosphate in acidocalcisome-like vesicles from oocytes and eggs of Periplaneta americana. Insect Biochem Mol Biol 39(3):198–206. doi:10.1016/j.ibmb.2008.11.003
Muller AD, Lichtenbeld HH, Blijham GH et al (1993) Mast cell lysate induces a procoagulant effect on endothelial cells. Thromb Res 72(3):263–267
Muller F, Mutch NJ, Schenk WA et al (2009) Platelet polyphosphates are proinflammatory and procoagulant mediators in vivo. Cell 139(6):1143–1156. doi:10.1016/j.cell.2009.11.001
Niyogi S, Jimenez V, Girard-Dias W et al (2015) Rab32 is essential for maintaining functional acidocalcisomes and for growth and infectivity of Trypanosoma cruzi. J Cell Sci 128:2363–2373. doi:10.1242/jcs.169466
Ogawa N, DeRisi J, Brown PO (2000) New components of a system for phosphate accumulation and polyphosphate metabolism in Saccharomyces cerevisiae revealed by genomic expression analysis. Mol Biol Cell 11(12):4309–4321
Oschatz C, Maas C, Lecher B et al (2011) Mast cells increase vascular permeability by heparin-initiated bradykinin formation in vivo. Immunity 34(2):258–268. doi:10.1016/j.immuni.2011.02.008
Patel S, Docampo R (2010) Acidic calcium stores open for business: expanding the potential for intracellular Ca2+ signaling. Trends Cell Biol 20(5):277–286. doi:10.1016/j.tcb.2010.02.003
Ramos IB, Miranda K, Pace DA et al (2010a) Calcium- and polyphosphate-containing acidic granules of sea urchin eggs are similar to acidocalcisomes, but are not the targets for NAADP. Biochem J 429(3):485–495. doi:10.1042/BJ20091956
Ramos IB, Miranda K, Ulrich P et al (2010b) Calcium- and polyphosphate-containing acidocalcisomes in chicken egg yolk. Biol Cell 102(7):421–434. doi:10.1042/BC20100011
Ramos I, Gomes F, Koeller CM et al (2011) Acidocalcisomes as calcium- and polyphosphate-storage compartments during embryogenesis of the insect Rhodnius prolixus Stahl. PLoS One 6(11):e27276. doi:10.1371/journal.pone.0027276
Rodrigues CO, Scott DA, Docampo R (1999a) Characterization of a vacuolar pyrophosphatase in Trypanosoma brucei and its localization to acidocalcisomes. Mol Cell Biol 19(11):7712–7723
Rodrigues CO, Scott DA, Docampo R (1999b) Presence of a vacuolar H+-pyrophosphatase in promastigotes of Leishmania donovani and its localization to a different compartment from the vacuolar H+-ATPase. Biochem J 340(Pt 3):759–766
Rodrigues CO, Ruiz FA, Vieira M et al (2002a) An acidocalcisomal exopolyphosphatase from Leishmania major with high affinity for short chain polyphosphate. J Biol Chem 277(52):50899–50906. doi:10.1074/jbc.M208940200
Rodrigues CO, Ruiz FA, Rohloff P et al (2002b) Characterization of isolated acidocalcisomes from Toxoplasma gondii tachyzoites reveals a novel pool of hydrolyzable polyphosphate. J Biol Chem 277(50):48650–48656. doi:10.1074/jbc.M208990200
Rohloff P, Rodrigues CO, Docampo R (2003) Regulatory volume decrease in Trypanosoma cruzi involves amino acid efflux and changes in intracellular calcium. Mol Biochem Parasitol 126(2):219–230
Rohloff P, Montalvetti A, Docampo R (2004) Acidocalcisomes and the contractile vacuole complex are involved in osmoregulation in Trypanosoma cruzi. J Biol Chem 279(50):52270–52281. doi:10.1074/jbc.M410372200
Rohloff P, Miranda K, Rodrigues JC et al (2011) Calcium uptake and proton transport by acidocalcisomes of Toxoplasma gondii. PLoS One 6(4):e18390. doi:10.1371/journal.pone.0018390
Rooney PJ, Ayong L, Tobin CM et al (2011) TgVTC2 is involved in polyphosphate accumulation in Toxoplasma gondii. Mol Biochem Parasitol 176(2):121–126. doi:10.1016/j.molbiopara.2010.12.012
Ruiz FA, Rodrigues CO, Docampo R (2001a) Rapid changes in polyphosphate content within acidocalcisomes in response to cell growth, differentiation, and environmental stress in Trypanosoma cruzi. J Biol Chem 276(28):26114–26121. doi:10.1074/jbc.M102402200
Ruiz FA, Marchesini N, Seufferheld M et al (2001b) The polyphosphate bodies of Chlamydomonas reinhardtii possess a proton-pumping pyrophosphatase and are similar to acidocalcisomes. J Biol Chem 276(49):46196–46203. doi:10.1074/jbc.M105268200
Ruiz FA, Lea CR, Oldfield E, Docampo R (2004a) Human platelet dense granules contain polyphosphate and are similar to acidocalcisomes of bacteria and unicellular eukaryotes. J Biol Chem J Biol Chem 279(43):44250–44257. doi:10.1074/jbc.M406261200
Ruiz FA, Luo S, Moreno SN, Docampo R (2004b) Polyphosphate content and fine structure of acidocalcisomes of Plasmodium falciparum. Microsc Microanal 10(5):563–567. doi:10.1017/S1431927604040875
Sahin A, Espiau B, Tetaud E et al (2008) The leishmania ARL-1 and Golgi traffic. PLoS One 3(2):e1620. doi:10.1371/journal.pone.0001620
Scott DA, Docampo R (2000) Characterization of isolated acidocalcisomes of Trypanosoma cruzi. J Biol Chem 275(31):24215–24221. doi:10.1074/jbc.M002454200
Scott DA, Docampo R, Dvorak JA et al (1997) In situ compositional analysis of acidocalcisomes in Trypanosoma cruzi. J Biol Chem 272(44):28020–28029
Sethuraman A, Rao NN, Kornberg A (2001) The endopolyphosphatase gene: essential in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 98(15):8542–8547. doi:10.1073/pnas.151269398
Seufferheld M, Vieira MC, Ruiz FA et al (2003) Identification of organelles in bacteria similar to acidocalcisomes of unicellular eukaryotes. J Biol Chem 278(32):29971–29978. doi:10.1074/jbc.M304548200
Seufferheld M, Lea CR, Vieira M et al (2004) The H+-pyrophosphatase of Rhodospirillum rubrum is predominantly located in polyphosphate-rich acidocalcisomes. J Biol Chem 279(49):51193–51202. doi:10.1074/jbc.M406099200
Shi X, Kornberg A (2005) Endopolyphosphatase in Saccharomyces cerevisiae undergoes post-translational activations to produce short-chain polyphosphates. FEBS Lett 579(9):2014–2018. doi:10.1016/j.febslet.2005.02.032
Smith SA, Mutch NJ, Baskar D et al (2006) Polyphosphate modulates blood coagulation and fibrinolysis. Proc Natl Acad Sci U S A 103(4):903–908. doi:10.1073/pnas.0507195103
Soares Medeiros LC, Gomes F, Maciel LR et al (2011) Volutin granules of Eimeria parasites are acidic compartments and have physiological and structural characteristics similar to acidocalcisomes. J Eukaryot Microbiol 58(5):416–423. doi:10.1111/j.1550-7408.2011.00565.x
Ulrich PN, Lander N, Kurup SP et al (2014) The acidocalcisome vacuolar transporter chaperone 4 catalyzes the synthesis of polyphosphate in insect-stages of Trypanosoma brucei and T. cruzi. J Eukaryot Microbiol 61(2):155–165. doi:10.1111/jeu.12093
Vercesi AE, Moreno SN, Docampo R (1994) Ca2+/H+ exchange in acidic vacuoles of Trypanosoma brucei. Biochem J 304(Pt 1):227–233
Whitehead MP, Hooley P, Brown MRW (2013) Horizontal transfer of bacterial polyphosphate kinases to eukaryotes: implications for the ice age and land colonisation. BMC Res Notes 6:221. doi:10.1186/1756-0500-6-221
Yagisawa F, Nishida K, Yoshida M et al (2009) Identification of novel proteins in isolated polyphosphate vacuoles in the primitive red alga Cyanidioschyzon merolae. Plant J: Cell Mol Biol 60(5):882–893. doi:10.1111/j.1365-313X.2009.04008.x
Zhang K, Hsu FF, Scott DA et al (2005) Leishmania salvage and remodelling of host sphingolipids in amastigote survival and acidocalcisome biogenesis. Mol Microbiol 55(5):1566–1578. doi:10.1111/j.1365-2958.2005.04493.x
Zhang H, Gomez-Garcia MR, Shi X et al (2007) Polyphosphate kinase 1, a conserved bacterial enzyme, in a eukaryote, Dictyostelium discoideum, with a role in cytokinesis. Proc Natl Acad Sci U S A 104(42):16486–16491. doi:10.1073/pnas.0706847104
Acknowledgments
Work in the author’s laboratory is supported by the US National Institutes of Health grants AI107663 and AI077538.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Docampo, R. (2016). Polyphosphate Storage and Function in Acidocalcisomes. In: Kulakovskaya, T., Pavlov, E., Dedkova, E. (eds) Inorganic Polyphosphates in Eukaryotic Cells. Springer, Cham. https://doi.org/10.1007/978-3-319-41073-9_3
Download citation
DOI: https://doi.org/10.1007/978-3-319-41073-9_3
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-41071-5
Online ISBN: 978-3-319-41073-9
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)