Abstract
Malaria has been present since ancient time and remains a major global health problem in developing countries. Plasmodium falciparum belongs to the phylum Apicomplexan, largely contain disease-causing parasites and characterized by the presence of apicoplast. It is a very essential organelle of P. falciparum responsible for the synthesis of key molecules required for the growth of the parasite. Indispensable nature of apicoplast makes it a potential drug target. Calcium signaling is important in the establishment of malaria parasite inside the host. It has been involved in invasion and egress of merozoites during the asexual life cycle of the parasite. Calcium signaling also regulates apicoplast metabolism. Therefore, in this review, we will focus on the role of apicoplast in malaria biology and its metabolic regulation through Ca++ signaling.
Similar content being viewed by others
References
Aboulaila, M., Munkhjargal, T., Sivakumar, T., Ueno, A., Nakano, Y., Yokoyama, M., Yoshinari, T., Nagano, D., Katayama, K., El-Bahy, N., et al. 2012. Apicoplast-targeting antibacterials inhibit the growth of Babesia parasites. Antimicrob. Agents Chemother. 56, 3196–3206.
Agrawal, S., Chung, D.W.D., Ponts, N., van Dooren, G.G., Prudhomme, J., Brooks, C.F., Rodrigues, E.M., Tan, J.C., Ferdig, M.T., Striepen, B., et al. 2013a. An apicoplast localized ubiquitylation system is required for the import of nuclear-encoded plastid proteins. PLoS Pathog. 9, e1003426–e1003426.
Agarwal, S., Singh, M.K., Garg, S., Chitnis, C.E., and Singh, S. 2013b. Ca2+-mediated exocytosis of subtilisin-like protease 1: a key step in egress of Plasmodium falciparum merozoites. Cell. Microbiol. 15, 910–921.
Alam, M.M., Solyakov, L., Bottrill, A.R., Flueck, C., Siddiqui, F.A., Singh, S., Mistry, S., Viskaduraki, M., Lee, K., and Hopp, C.S. 2015. Phosphoproteomics reveals malaria parasite Protein Kinase G as a signalling hub regulating egress and invasion. Nat. Commun. 6, 7285.
Alves, E., Bartlett, P.J., Garcia, C.R.S., and Thomas, A.P. 2011. Melatonin and IP3-induced Ca2+ release from intracellular stores in the malaria parasite Plasmodium falciparum within infected red blood cells. J. Biol. Chem. 286, 5905–5912.
Bansal, A., Singh, S., More, K.R., Hans, D., Nangalia, K., Yogavel, M., Sharma, A., and Chitnis, C.E. 2013. Characterization of Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) and its role in microneme secretion during erythrocyte invasion. J. Biol. Chem. 288, 1590–1602.
Berridge, M.J., Lipp, P., and Bootman, M.D. 2000. The versatility and universality of calcium signalling. Nat. Rev. Mol. Cell. Biol. 1, 11–21.
Billker, O., Dechamps, S., Tewari, R., Wenig, G., Franke-Fayard, B., and Brinkmann, V. 2004. Calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in a malaria parasite. Cell. 117, 503–514.
Blackman, M.J. 2008. Malarial proteases and host cell egress: an ‘emerging’cascade. Cell. Microbiol. 10, 1925–1934.
Bootman, M.D., Collins, T.J., Peppiatt, C.M., Prothero, L.S., Mac-Kenzie, L., De Smet, P., Travers, M., Tovey, S.C., Seo, J.T., Berridge, M.J., et al. 2001. Calcium signalling–an overview. Semin. Cell. Dev. Biol. 12, 3–10.
Bozdech, Z., Llinas, M., Pulliam, B.L., Wong, E.D., Zhu, J., and DeRisi, J.L. 2003. The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum. PLoS Biol. 1, e5–E5.
Brochet, M., Collins, M.O., Smith, T.K., Thompson, E., Sebastian, S., Volkmann, K., Schwach, F., Chappell, L., Gomes, A.R., and Berriman, M. 2014. Phosphoinositide metabolism links cGMP-dependent protein kinase G to essential Ca2+ signals at key decision points in the life cycle of malaria parasites. PLoS Biol. 12, e1001806.
Budimulja, A.S., Syafruddin, Tapchaisri, P., Wilairat, P., and Marzuki, S. 1997. The sensitivity of Plasmodium protein synthesis to prokaryotic ribosomal inhibitors. Mol. Biochem. Parasitol. 84, 137–141.
Carruthers, V.B. and Sibley, L.D. 1999. Mobilization of intracellular calcium stimulates microneme discharge in Toxoplasma gondii. Mol. Microbiol. 31, 421–428.
Cheemadan, S., Ramadoss, R., and Bozdech, Z. 2014. Role of calcium signaling in the transcriptional regulation of the apicoplast genome of Plasmodium falciparum. Biomed. Res. Int. 2014, 869401–869401.
Clapham, D.E. 2007. Calcium signaling. Cell. 131, 1047–1058.
Cruz, L.N., Wu, Y., Ulrich, H., Craig, A.G., and Garcia, C.R. 2016. Tumor necrosis factor reduces Plasmodium falciparum growth and activates calcium signaling in human malaria parasites. Biochim. Biophys. Acta. 1860, 1489–1497.
Dahl, E.L. and Rosenthal, P.J. 2008. Apicoplast translation, transcription and genome replication: targets for antimalarial antibiotics. Trends Parasitol. 24, 279–284.
Dahl, E.L., Shock, J.L., Shenai, B.R., Gut, J., DeRisi, J.L., and Rosenthal, P.J. 2006. Tetracyclines specifically target the apicoplast of the malaria parasite Plasmodium falciparum. Antimicrob. Agents Chemother. 50, 3124–3131.
Dawn, A., Singh, S., More, K.R., Siddiqui, F.A., Pachikara, N., Ramdani, G., Langsley, G., and Chitnis, C.E. 2014. The central role of cAMP in regulating Plasmodium falciparum merozoite invasion of human erythrocytes. PLoS Pathog. 10, e1004520.
Divo, A.A., Sartorelli, A.C., Patton, C.L., and Bia, F.J. 1988. Activity of fluoroquinolone antibiotics against Plasmodium falciparum in vitro. Antimicrob. Agents Chemother. 32, 1182–1186.
Docampo, R., de Souza, W., Miranda, K., Rohloff, P., and Moreno, S.N.J. 2005. Acidocalcisomes? conserved from bacteria to man. Nat. Rev. Microbiol. 3, 251–261.
Dvorin, J.D., Martyn, D.C., Patel, S.D., Grimley, J.S., Collins, C.R., Hopp, C.S., Bright, A.T., Westenberger, S., Winzeler, E., and Blackman, M.J. 2010. A plant-like kinase in Plasmodium falciparum regulates parasite egress from erythrocytes. Science 328, 910–912.
Eckstein-Ludwig, U., Webb, R.J., Van Goethem, I.D.A., East, J.M., Lee, A.G., Kimura, M., O'Neill, P.M., Bray, P.G., Ward, S.A., and Krishna, S. 2003. Artemisinins target the SERCA of Plasmodium falciparum. Nature 424, 957–961.
Foth, B.J. and McFadden, G.I. 2003. The apicoplast: a plastid in Plasmodium falciparum and other Apicomplexan parasites. Int. Rev. Cytol. 224, 57–110.
Furuyama, W., Enomoto, M., Mossaad, E., Kawai, S., Mikoshiba, K., and Kawazu, S.-i. 2014. An interplay between 2 signaling pathways: melatonin-cAMP and IP3-Ca2+ signaling pathways control intraerythrocytic development of the malaria parasite Plasmodium falciparum. Biochem. Biophys. Res. Commun. 446, 125–131.
Gao, X., Gunalan, K., Yap, S.S.L., and Preiser, P.R. 2013. Triggers of key calcium signals during erythrocyte invasion by Plasmodium falciparum. Nat. Commun. 4, 2862.
Gardner, M.J., Feagin, J.E., Moore, D.J., Spencer, D.F., Gray, M.W., Williamson, D.H., and Wilson, R.J.M. 1991a. Organisation and expression of small subunit ribosomal RNA genes encoded by a 35-kilobase circular DNA in Plasmodium falciparum. Mol. Biochem. Parasitol. 48, 77–88.
Gardner, M.J., Williamson, D.H., and Wilson, R.J.M. 1991b. A circular DNA in malaria parasites encodes an RNA polymerase like that of prokaryotes and chloroplasts. Mol. Biochem. Parasitol. 44, 115–123.
Jones, M.L., Cottingham, C., and Rayner, J.C. 2009. Effects of calcium signaling on Plasmodium falciparum erythrocyte invasion and post-translational modification of gliding-associated protein 45 (PfGAP45). Mol. Biochem. Parasitol. 168, 55–62.
Karkare, S., Yousafzai, F., Mitchenall, L.A., and Maxwell, A. 2012. The role of Ca2+ in the activity of Mycobacterium tuberculosis DNA gyrase. Nucleic Acids Res. 40, 9774–9787.
Krishna, S., Woodrow, C., Webb, R., Penny, J., Takeyasu, K., Kimura, M., and East, J.M. 2001. Expression and functional characterization of a Plasmodium falciparum Ca2+-ATPase (PfATP4) belonging to a subclass unique to apicomplexan organisms. J. Biol. Chem. 276, 10782–10787.
Kumar, P., Tripathi, A., Ranjan, R., Halbert, J., Gilberger, T., Doerig, C., and Sharma, P. 2014. Regulation of Plasmodium falciparum development by calcium-dependent protein kinase 7 (PfCDPK7). J. Biol. Chem. 289, 20386–20395.
Lewit-Bentley, A. and Réty, S. 2000. EF-hand calcium-binding proteins. Curr. Opin. Struct. Biol. 10, 637–643.
Li, J., Matsuoka, H., Mitamura, T., and Horii, T. 2002. Characterization of proteases involved in the processing of Plasmodium falciparum serine repeat antigen (SERA). Mol. Biochem. Parasitol. 120, 177–186.
Lim, L. and McFadden, G.I. 2010. The evolution, metabolism and functions of the apicoplast. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 365, 749–763.
Lin, T.Y., Nagano, S., and Heddle, J.G. 2015. Functional analyses of the Toxoplasma gondii DNA gyrase holoenzyme: a janus topoisomerase with supercoiling and decatenation abilities. Sci. Rep. 5, 14491.
Lourido, S. and Moreno, S.N.J. 2015. The calcium signaling toolkit of the Apicomplexan parasites Toxoplasma gondii and Plasmodium spp. Cell. Calcium. 57, 186–193.
Lovett, J.L., Marchesini, N., Moreno, S.N.J., and Sibley, L.D. 2002. Toxoplasma gondii microneme secretion involves intracellular Ca2+ release from inositol 1, 4, 5-triphosphate (IP3)/ryanodinesensitive stores. J. Biol. Chem. 277, 25870–25876.
McFadden, G.I. 1996. Plastid in human parasites. Nature 381, 482–482.
McFadden, G.I. 2011. The apicoplast. Protoplasma 248, 641–650.
Moore, P., Preiser, P., and Williamson, D. 2002. The plastid DNA of the malaria parasite Plasmodium falciparum is replicated by two mechanisms. Mol. Microbiol. 44, 533–533.
Moreno, S.N. and Docampo, R. 2003. Calcium regulation in protozoan parasites. Curr. Opin. Microbiol. 6, 359–364.
Nagamune, K., Moreno, S.N., Chini, E.N., and Sibley, L.D. 2008. Calcium regulation and signaling in Apicomplexan parasites. In Burleigh, B.A. and Soldati-Favre, D. (eds.), Molecular Mechanisms of Parasite Invasion: Subcellular Biochemistry, pp. 70–81. Springer New York, New York, NY, USA.
Nagamune, K. and Sibley, L.D. 2006. Comparative genomic and phylogenetic analyses of calcium ATPases and calcium-regulated proteins in the apicomplexa. Mol. Biol. Evol. 23, 1613–1627.
Nagano, S., Lin, T.Y., Edula, J., and Heddle, J. 2014. Unique features of apicoplast DNA gyrases from Toxoplasma gondii and Plasmodium falciparum. BMC Bioinformatics 15, 416–416.
Nagata, T., Iizumi, S., Satoh, K., Ooka, H., Kawai, J., Carninci, P., Hayashizaki, Y., Otomo, Y., Murakami, K., and Matsubara, K. 2004. Comparative analysis of plant and animal calcium signal transduction element using plant full-length cDNA data. Mol. Biol. Evol. 21, 1855–1870.
Nisbet, R.E.R., Kurniawan, D.P., Bowers, H.D., and Howe, C.J. 2016. Transcripts in the Plasmodium Apicoplast undergo cleavage at tRNAs and editing, and include antisense sequences. Protist 167, 377–388.
Nisbet, R.E.R. and McKenzie, J.L. 2016. Transcription of the apicoplast genome. Mol. Biochem. Parasitol. 210-1, 5–9.
Okamoto, N., Spurck, T.P., Goodman, C.D., and McFadden, G.I. 2009. Apicoplast and mitochondrion in gametocytogenesis of Plasmodium falciparum. Eukaryot. Cell 8, 128–132.
Pukrittayakamee, S., Clemens, R., Chantra, A., Nontprasert, A., Luknam, T., Looareesuwan, S., and White, N.J. 2001. Therapeutic responses to antibacterial drugs in vivax malaria. Trans. R. Soc. Trop. Med. Hyg. 95, 524–528.
Ranjan, R., Ahmed, A., Gourinath, S., and Sharma, P. 2009. Dissection of mechanisms involved in the regulation of Plasmodium falciparum calcium-dependent protein kinase 4. J. Biol. Chem. 284, 15267–15276.
Robson, K.J.H. and Jennings, M.W. 1991. The structure of the calmodulin gene of Plasmodium falciparum. Mol. Biochem. Parasitol. 46, 19–34.
Schuck, D.C., Jordão, A.K., Nakabashi, M., Cunha, A.C., Ferreira, V.F., and Garcia, C.R. 2014. Synthetic indole and melatonin derivatives exhibit antimalarial activity on the cell cycle of the human malaria parasite Plasmodium falciparum. Eur. J. Med. Chem. 78, 375–382.
Siden-Kiamos, I., Ecker, A., Nybäck, S., Louis, C., Sinden, R.E., and Billker, O. 2006. Plasmodium berghei calcium-dependent protein kinase 3 is required for ookinete gliding motility and mosquito midgut invasion. Mol. Microbiol. 60, 1355–1363.
Singh, S., Alam, M.M., Pal-Bhowmick, I., Brzostowski, J.A., and Chitnis, C.E. 2010. Distinct external signals trigger sequential release of apical organelles during erythrocyte invasion by malaria parasites. PLoS Pathog. 6, e1000746–e1000746.
Spillman, N.J., Allen, R.J.W., McNamara, C.W., Yeung, B.K.S., Winzeler, E.A., Diagana, T.T., and Kirk, K. 2013. Na+ regulation in the malaria parasite Plasmodium falciparum involves the cation ATPase PfATP4 and is a target of the spiroindolone antimalarials. Cell Host Microbe 13, 227–237.
Tonkin, C.J., Foth, B.J., Ralph, S.A., Struck, N., Cowman, A.F., and McFadden, G.I. 2008. Evolution of malaria parasite plastid targeting sequences. Proc. Natl. Acad. Sci. USA 105, 4781–4785.
Vaid, A., Thomas, D.C., and Sharma, P. 2008. Role of Ca2+/calmodulin-PfPKB signaling pathway in erythrocyte invasion by Plasmodium falciparum. J. Biol. Chem. 283, 5589–5597.
Waller, R.F. and McFadden, G.I. 2005. The apicoplast: A review of the derived plastid of apicomplexan parasites. Curr. Issues Mol. Biol. 7, 57–80.
Wilson, R.J.M., Denny, P.W., Preiser, P.R., Rangachari, K., Roberts, K., Roy, A., Whyte, A., Strath, M., Moore, D.J., Moore, P.W., et al. 1996. Complete gene map of the plastid-like DNA of the malaria parasite Plasmodium falciparum. J. Mol. Biol. 261, 155–172.
World Health Organization. 2015. WHO word maleria report 2015. WHO.
Wright, G.J. and Rayner, J.C. 2014. Plasmodium falciparum erythrocyte invasion: combining function with immune evasion. PLoS Pathog. 10, e1003943.
Yeoh, S., O'Donnell, R.A., Koussis, K., Dluzewski, A.R., Ansell, K.H., Osborne, S.A., Hackett, F., Withers-Martinez, C., Mitchell, G.H., Bannister, L.H., et al. 2007. Subcellular discharge of a serine protease mediates release of invasive malaria parasites from host erythrocytes. Cell 131, 1072–1083.
Zuegge, J., Ralph, S., Schmuker, M., McFadden, G.I., and Schneider, G. 2001. Deciphering apicoplast targeting signals–feature extraction from nuclear-encoded precursors of Plasmodium falciparum apicoplast proteins. Gene 280, 19–26.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Rai, P., Sharma, D., Soni, R. et al. Plasmodium falciparum apicoplast and its transcriptional regulation through calcium signaling. J Microbiol. 55, 231–236 (2017). https://doi.org/10.1007/s12275-017-6525-1
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12275-017-6525-1