8. Siden-Kiamos I, Ecker A, Nyba¨ck S, Louis C, Sinden RE, et al. (2006) Plasmodium berghei calcium-dependent protein kinase 3 is required for ookinete gliding motility and mosquito midgut invasion. Mol Microbiol 60: 1355–1363. doi:10.1111/j.1365-2958.2006.05189.x. 9. Ishino T, Orito Y, Chinzei Y, Yuda M (2006) A calcium-dependent protein kinase regulates Plasmodium ookinete access to the midgut epithelial cell. Mol Microbiol 59: 1175–1184. doi:10.1111/j.1365-2958.2005.05014.x. 10. Wetzel DM, Chen LA, Ruiz FA, Moreno SNJ, Sibley LD (2004) Calcium- mediated protein secretion potentiates motility in Toxoplasma gondii. J Cell Sci 117: 5739–5748. doi:10.1242/jcs.01495. 11. Sibley LD (2004) Intracellular parasite invasion strategies. Science 304: 248– 253. doi:10.1126/science.1094717. 12. Billker O, Dechamps S, Tewari R, Wenig G (2004) Calcium and a calcium- dependent protein kinase regulate gamete formation and mosquito transmission in a malaria parasite. Cell. 13. Lovett JL, Sibley LD (2003) Intracellular calcium stores in Toxoplasma gondii govern invasion of host cells. J Cell Sci 116: 3009–3016. doi:10.1242/jcs.00596. 14. Carruthers VB, Giddings OK, Sibley LD (1999) Secretion of micronemal proteins is associated with toxoplasma invasion of host cells. Cell Microbiol 1: 225–235. 15. Billker O, Lindo V, Panico M, Etienne AE, Paxton T, et al. (1998) Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito. Nature 392: 289–292. doi:10.1038/32667. 16. Dvorin JD, Martyn DC, Patel SD, Grimley JS, Collins CR, et al. (2010) A plant- like kinase in Plasmodium falciparum regulates parasite egress from erythrocytes. Science 328: 910–912. doi:10.1126/science.1188191. 17. Singh S, Alam MM, Pal-Bhowmick I, Brzostowski JA, Chitnis CE (2010) Distinct external signals trigger sequential release of apical organelles during erythrocyte invasion by malaria parasites. PLoS Pathog 6: e1000746. doi:10.1371/journal.ppat.1000746. 18. Vaid A, Thomas DC, Sharma P (2008) Role of Ca2+/calmodulin-PfPKB signaling pathway in erythrocyte invasion by Plasmodium falciparum. J Biol Chem 283: 5589–5597. doi:10.1074/jbc.M708465200. 19. Biagini GA, Bray PG, Spiller DG, White MRH, Ward SA (2003) The digestive food vacuole of the malaria parasite is a dynamic intracellular Ca2+ store. J Biol Chem 278: 27910–27915. doi:10.1074/jbc.M304193200. 20. Ch’ng J-H, Liew K, Goh AS-P, Sidhartha E, Tan KS-W (2011) Drug-induced permeabilization of parasite’s digestive vacuole is a key trigger of programmed cell death in Plasmodium falciparum. Cell Death Dis 2: e216. doi:10.1038/ cddis.2011.97. 21. Maruyama T, Kanaji T, Nakade S, Kanno T, Mikoshiba K (1997) 2APB, 2- aminoethoxydiphenyl borate, a membrane-penetrable modulator of Ins(1,4,5)P3-induced Ca2+ release. J Biochem 122: 498–505. 22. Bilmen JG, Michelangeli F (2002) Inhibition of the type 1 inositol 1,4,5- trisphosphate receptor by 2-aminoethoxydiphenylborate. Cell Signal 14: 955– 960. 23. Beraldo FH, Mikoshiba K, Garcia CRS (2007) Human malarial parasite, Plasmodium falciparum, displays capacitative calcium entry: 2-aminoethyl diphenylborinate blocks the signal transduction pathway of melatonin action on the P. falciparum cell cycle. J Pineal Res 43: 360–364. doi:10.1111/j.1600- 079X.2007.00486.x. 24. Beraldo FH, Almeida FM, da Silva AM, Garcia CRS (2005) Cyclic AMP and calcium interplay as second messengers in melatonin-dependent regulation of Plasmodium falciparum cell cycle. J Cell Biol 170: 551–557. doi:10.1083/ jcb.200505117. 25. Hotta CT, Markus RP, Garcia CRS (2003) Melatonin and N-acetyl-serotonin cross the red blood cell membrane and evoke calcium mobilization in malarial parasites. Braz J Med Biol Res 36: 1583–1587. doi:10.1590/S0100- 879X2003001100016. 26. Nagamune K, Moreno SN, Chini EN, Sibley LD (2008) Calcium regulation and signaling in apicomplexan parasites. Subcell Biochem 47: 70–81. 27. Moreno SNJ, Ayong L, Pace DA (2011) Calcium storage and function in apicomplexan parasites. Essays Biochem 51: 97–110. doi:10.1042/bse0510097. 28. Passos AP, Garcia CR (1997) Characterization of Ca2+ transport activity associated with a non-mitochondrial calcium pool in the rodent malaria parasite P. chabaudi. Biochem Mol Biol Int 42: 919–925. 29. Lehane AM, Hayward R, Saliba KJ, Kirk K (2008) A verapamil-sensitive chloroquine-associated H+ leak from the digestive vacuole in chloroquine- resistant malaria parasites. J Cell Sci 121: 1624–1632. doi:10.1242/jcs.016758. 30. van Schalkwyk DA, Chan XWA, Misiano P, Gagliardi S, Farina C, et al. (2010) Inhibition of Plasmodium falciparum pH regulation by small molecule indole derivatives results in rapid parasite death. Biochem Pharmacol 79: 1291–1299. doi:10.1016/j.bcp.2009.12.025. Plasmodium Ca2+ Oscillation in the Blood Stage 31. van Dooren GG, Marti M, Tonkin CJ, Stimmler LM, Cowman AF, et al. (2005) Development of the endoplasmic reticulum, mitochondrion and apicoplast during the asexual life cycle of Plasmodium falciparum. Mol Microbiol 57: 405– 419. doi:10.1111/j.1365-2958.2005.04699.x. 32. Mouray E, Moutiez M, Girault S, Sergheraert C, Florent I, et al. (2007) Biochemical properties and cellular localization of Plasmodium falciparum protein disulfide isomerase. Biochimie 89: 337–346. doi:10.1016/j.bio- chi.2006.11.001. 33. Kumar N, Koski G, Harada M, Aikawa M, Zheng H (1991) Induction and localization of Plasmodium falciparum stress proteins related to the heat shock protein 70 family. Mol Biochem Parasitol 48: 47–58. 34. Gratraud P, Huws E, Falkard B, Adjalley S, Fidock DA, et al. (2009) Oleic acid biosynthesis in Plasmodium falciparum: characterization of the stearoyl-CoA desaturase and investigation as a potential therapeutic target. PLoS ONE 4: e6889. doi:10.1371/journal.pone.0006889. 35. Bannister LH, Hopkins JM, Fowler RE, Krishna S, Mitchell GH (2000) Ultrastructure of rhoptry development in Plasmodium falciparum erythrocytic schizonts. Parasitology 121 (Pt 3): 273–287. 36. Maeno Y, Toyoshima T, Fujioka H, Ito Y, Meshnick SR, et al. (1993) Morphologic effects of artemisinin in Plasmodium falciparum. Am J Trop Med Hyg 49: 485–491. 37. Eckstein-Ludwig U, Webb RJ, Van Goethem IDA, East JM, Lee AG, et al. (2003) Artemisinins target the SERCA of Plasmodium falciparum. Nature 424: 957–961. doi:10.1038/nature01813. 38. Bola B, Allan V (2009) How and why does the endoplasmic reticulum move? Biochem Soc Trans 37: 961–965. doi:10.1042/BST0370961. 39. Baumann O, Walz B (2001) Endoplasmic reticulum of animal cells and its organization into structural and functional domains. Int Rev Cytol 205: 149– 214. 40. Schro¨ der M, Kaufman RJ (2005) THE MAMMALIAN UNFOLDED PROTEIN RESPONSE. Annu Rev Biochem 74: 739–789. doi:10.1146/ annurev.biochem.73.011303.074134. 41. Kim I, Xu W, Reed JC (2008) Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat Rev Drug Discov 7: 1013– 1030. doi:10.1038/nrd2755. 42. Bezprozvanny I (2009) Calcium signaling and neurodegenerative diseases. Trends in Molecular Medicine 15: 89–100. doi:10.1016/j.molmed.2009.01.001. 43. Berridge MJ (2010) Calcium hypothesis of Alzheimer’s disease. Pflugers Arch 459: 441–449. doi:10.1007/s00424-009-0736-1. 44. Talman AM, Domarle O, McKenzie FE, Ariey F, Robert V (2004) Gametocytogenesis: the puberty of Plasmodium falciparum. Malar J 3: 24. doi:10.1186/1475-2875-3-24. 45. Read LK, Mikkelsen RB (1991) Comparison of adenylate cyclase and cAMP- dependent protein kinase in gametocytogenic and nongametocytogenic clones of Plasmodium falciparum. J Parasitol 77: 346–352. 46. Kaushal DC, Carter R, Miller LH, Krishna G (1980) Gametocytogenesis by malaria parasites in continuous culture. Nature 286: 490–492. 47. Inselburg J (1983) Stage-Specific Inhibitory Effect of Cyclic AMP on Asexual Maturation and Gametocyte Formation of Plasmodium falciparum. 48. Brockelman CR (1982) Conditions favoring gametocytogenesis in the continuous culture of Plasmodium falciparum. The Journal of protozoology 29: 454–458. 49. Trager W, GILL GS (1989) Plasmodium falciparum gametocyte formation in vitro: its stimulation by phorbol diesters and by 8-bromo cyclic adenosine monophosphate. The Journal of protozoology 36: 451–454. 50. Alves E, Bartlett PJ, Garcia CRS, Thomas AP (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. doi:10.1074/jbc.M110.188474. 51. Hotta CT, Gazarini ML, Beraldo FH, Varotti FP, Lopes C, et al. (2000) Calcium-dependent modulation by melatonin of the circadian rhythm in malarial parasites. Nat Cell Biol 2: 466–468. doi:10.1038/35017112. 52. Nagata T, Iizumi S, Satoh K, Ooka H, Kawai J, et al. (2004) Comparative analysis of plant and animal calcium signal transduction element using plant full- length cDNA data. Mol Biol Evol 21: 1855–1870. doi:10.1093/molbev/msh197. 53. Trager W, Jensen JB (1976) Human malaria parasites in continuous culture. Science 193: 673–675. 54. Lambros C, Vanderberg JP (1979) Synchronization of Plasmodium falciparum erythrocytic stages in culture. J Parasitol 65: 418–420. 55. Kawai S, Kano S, Chang C, Suzuki M (1996) The effects of pyronaridine on the morphology of Plasmodium falciparum in Aotus trivirgatus. Am J Trop Med Hyg 55: 223–229. PLoS ONE | www.plosone.org 12 July 2012 | Volume 7 | Issue 7 | e39499