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  • Review Article
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Cell division in apicomplexan parasites

Nature Reviews Microbiology volume 12, pages 125–136 (2014)Cite this article

Subjects

Key Points

  • Apicomplexa are eukaryotic parasites that cause important human and veterinary diseases, such as malaria, toxoplasmosis and cryptosporidiosis.

  • Apicomplexa replicate within the cells of their hosts by highly flexible and adaptable mechanisms, which can generate thousands of progeny to spread the infection.

  • The cell division of Apicomplexa occurs by closed mitosis of the nucleus and budding of daughter cells.

  • The regulation of apicomplexan cell cycle progression occurs at a global level throughout the cytoplasm and at a local level for each individual nucleus. Control is exerted by the activity of regulatory kinases, by modulating transcription, translation and protein stability and by the presence of physical tethers.

  • The apicomplexan nucleus is highly structured into defined nuclear territories. Centromeres and telomeres occupy defined positions, which are closely connected to the position of the centrosome to ensure genome and epigenome integrity during division.

  • Daughter cells are assembled in a stepwise and highly ordered process that is temporally and spatially guided by cytoskeletal self-organization and that is physically linked to the centrosome.

  • The centrosome emerges as a central regulatory location for the progression and completion of cell division in Apicomplexa.

Abstract

Toxoplasma gondii and Plasmodium falciparum are important human pathogens. These parasites and many of their apicomplexan relatives undergo a complex developmental process in the cells of their hosts, which includes genome replication, cell division and the assembly of new invasive stages. Apicomplexan cell cycle progression is both globally and locally regulated. Global regulation is carried out throughout the cytoplasm by diffusible factors that include cell cycle-specific kinases, cyclins and transcription factors. Local regulation acts on individual nuclei and daughter cells that are developing inside the mother cell. We propose that the centrosome is a master regulator that physically tethers cellular components and that provides spatial and temporal control of apicomplexan cell division.

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Figure 1: Organizational principles of apicomplexan replication.
Figure 2: Replication cycles of different apicomplexan species.
Figure 3: Apicomplexa divide by closed mitosis.
Figure 4: Electron-microscopic detail of mitosis and budding in T. gondii
Figure 5: Organization of parasite budding.

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References

  1. Cowman, A. F., Berry, D. & Baum, J. The cellular and molecular basis for malaria parasite invasion of the human red blood cell. J. Cell Biol. 198, 961–971 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Sibley, L. D. Invasion and intracellular survival by protozoan parasites. Immunol. Rev. 240, 72–91 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Sheffield, H. G. & Melton, M. L. The fine structure and reproduction of Toxoplasma gondii. J. Parasitol. 54, 209–226 (1968).

    CAS  PubMed  Google Scholar 

  4. Dubremetz, J. F. Ultrastructural study of schizogonic mitosis in the coccidian, Eimeria necatrix (Johnson 1930). J. Ultrastruct. Res. 42, 354–376 (1973).

    CAS  PubMed  Google Scholar 

  5. Sinden, R. E. & Smalley, M. E. Gametocytogenesis of Plasmodium falciparum in vitro: the cell-cycle. Parasitology 79, 277–296 (1979).

    CAS  PubMed  Google Scholar 

  6. Schrevel, J., Asfaux-Foucher, G. & Bafort, J. M. Ultrastructural study of multiple mitoses during sporogony of Plasmodium b. berghei. J. Ultrastruct. Res. 59, 332–350 (1977).

    CAS  PubMed  Google Scholar 

  7. Striepen, B., Jordan, C. N., Reiff, S. & van Dooren, G. G. Building the perfect parasite: cell division in apicomplexa. PLoS Pathog. 3, e78 (2007).

    PubMed  PubMed Central  Google Scholar 

  8. Gupta, A., Mehra, P. & Dhar, S. K. Plasmodium falciparum origin recognition complex subunit 5: functional characterization and role in DNA replication foci formation. Mol. Microbiol. 69, 646–665 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Arnot, D. E., Ronander, E. & Bengtsson, D. C. The progression of the intra-erythrocytic cell cycle of Plasmodium falciparum and the role of the centriolar plaques in asynchronous mitotic division during schizogony. Int. J. Parasitol. 41, 71–80 (2011). This study shows that cell cycle progression is asynchronous during P. falciparum schizogony.

    CAS  PubMed  Google Scholar 

  10. Gerald, N., Mahajan, B. & Kumar, S. Mitosis in the human malaria parasite Plasmodium falciparum. Eukaryot. Cell 10, 474–482 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Radke, J. R. et al. Defining the cell cycle for the tachyzoite stage of Toxoplasma gondii. Mol. Biochem. Parasitol. 115, 165–175 (2001).

    CAS  PubMed  Google Scholar 

  12. Radke, J. R. & White, M. W. A cell cycle model for the tachyzoite of Toxoplasma gondii using the Herpes simplex virus thymidine kinase. Mol. Biochem. Parasitol. 94, 237–247 (1998).

    CAS  PubMed  Google Scholar 

  13. Nishi, M., Hu, K., Murray, J. M. & Roos, D. S. Organellar dynamics during the cell cycle of Toxoplasma gondii. J. Cell Sci. 121, 1559–1568 (2008).

    CAS  PubMed  Google Scholar 

  14. Bornens, M. The centrosome in cells and organisms. Science 335, 422–426 (2012).

    CAS  PubMed  Google Scholar 

  15. Bornens, M., Paintrand, M., Berges, J., Marty, M. C. & Karsenti, E. Structural and chemical characterization of isolated centrosomes. Cell. Motil. Cytoskeleton 8, 238–249 (1987).

    CAS  PubMed  Google Scholar 

  16. Mardin, B. R. & Schiebel, E. Breaking the ties that bind: new advances in centrosome biology. J. Cell Biol. 197, 11–18 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Dubremetz, J. F. L'ultrastructure du centriole et du centrocone chez la coccidie Eimeria necatrix. Étude au cours de la schizogonie. J. Microscopie 12, 453–458 (1971) (in French).

    Google Scholar 

  18. Morrissette, N. S. & Sibley, L. D. Cytoskeleton of apicomplexan parasites. Microbiol. Mol. Biol. Rev. 66, 21–38 (2002).

    PubMed  PubMed Central  Google Scholar 

  19. Mahajan, B. et al. Centrins, cell cycle regulation proteins in human malaria parasite Plasmodium falciparum. J. Biol. Chem. 283, 31871–31883 (2008).

    CAS  PubMed  Google Scholar 

  20. Sinden, R. E. Gametocytogenesis of Plasmodium falciparum in vitro: an electron microscopic study. Parasitology 84, 1–11 (1982).

    CAS  PubMed  Google Scholar 

  21. Read, M., Sherwin, T., Holloway, S. P., Gull, K. & Hyde, J. E. Microtubular organization visualized by immunofluorescence microscopy during erythrocytic schizogony in Plasmodium falciparum and investigation of post-translational modifications of parasite tubulin. Parasitology 106, 223–232 (1993).

    PubMed  Google Scholar 

  22. Vaishnava, S. et al. Plastid segregation and cell division in the apicomplexan parasite Sarcocystis neurona. J. Cell Sci. 118, 3397–3407 (2005).

    CAS  PubMed  Google Scholar 

  23. Speer, C. A. & Dubey, J. P. Ultrastructure of shizonts and merozoites of Sarcocystis falcatula in the lungs of budgerigars (Melopsittacus undulatus). J. Parasitol. 85, 630–637 (1999).

    CAS  PubMed  Google Scholar 

  24. Ferguson, D. J., Hutchison, W. M., Dunachie, J. F. & Siim, J. C. Ultrastructural study of early stages of asexual multiplication and microgametogony of Toxoplasma gondii in the small intestine of the cat. Acta Pathol. Microbiol. Scand. B Microbiol. Immunol. 82, 167–181 (1974).

    CAS  PubMed  Google Scholar 

  25. Heussler, V. T. et al. Hijacking of host cell IKK signalosomes by the transforming parasite Theileria. Science 298, 1033–1036 (2002).

    CAS  PubMed  Google Scholar 

  26. von Schubert, C. et al. The transforming parasite Theileria co-opts host cell mitotic and central spindles to persist in continuously dividing cells. PLoS Biol. 8, e1000499 (2010).

    PubMed  PubMed Central  Google Scholar 

  27. Romano, J. D., Bano, N. & Coppens, I. New host nuclear functions are not required for the modifications of the parasitophorous vacuole of Toxoplasma. Cell. Microbiol. 10, 465–476 (2008).

    CAS  PubMed  Google Scholar 

  28. Walker, M. E. et al. Toxoplasma gondii actively remodels the microtubule network in host cells. Microbes Infect. 10, 1440–1449 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Malumbres, M. et al. Cyclin-dependent kinases: a family portrait. Nature Cell Biol. 11, 1275–1276 (2009).

    CAS  PubMed  Google Scholar 

  30. Morgan, D. O. et al. Control of eukaryotic cell cycle progression by phosphorylation of cyclin-dependent kinases. Cancer J. Sci. Am. 4, S77–S83 (1998).

    PubMed  Google Scholar 

  31. Morgan, D. O. Cyclin-dependent kinases: engines, clocks, and microprocessors. Annu. Rev. Cell Dev. Biol. 13, 261–291 (1997).

    CAS  PubMed  Google Scholar 

  32. Mocciaro, A. & Rape, M. Emerging regulatory mechanisms in ubiquitin-dependent cell cycle control. J. Cell Sci. 125, 255–263 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Doerig, C., Endicott, J. & Chakrabarti, D. Cyclin-dependent kinase homologues of Plasmodium falciparum. Int. J. Parasitol. 32, 1575–1585 (2002).

    CAS  PubMed  Google Scholar 

  34. Halbert, J. et al. A Plasmodium falciparum transcriptional cyclin-dependent kinase-related kinase with a crucial role in parasite proliferation associates with histone deacetylase activity. Eukaryot. Cell 9, 952–959 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Gubbels, M. J., White, M. & Szatanek, T. The cell cycle and Toxoplasma gondii cell division: tightly knit or loosely stitched? Int. J. Parasitol. 38, 1343–1358 (2008).

    CAS  PubMed  Google Scholar 

  36. Kvaal, C. A., Radke, J. R., Guerini, M. N. & White, M. W. Isolation of a Toxoplasma gondii cyclin by yeast two-hybrid interactive screen. Mol. Biochem. Parasitol. 120, 187–194 (2002).

    CAS  PubMed  Google Scholar 

  37. Dorin-Semblat, D. et al. Plasmodium falciparum NIMA-related kinase Pfnek-1: sex specificity and assessment of essentiality for the erythrocytic asexual cycle. Microbiology 157, 2785–2794 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Le Roch, K. G. et al. Discovery of gene function by expression profiling of the malaria parasite life cycle. Science 301, 1503–1508 (2003).

    CAS  PubMed  Google Scholar 

  39. Bozdech, Z. et al. The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum. PLoS Biol. 1, e5 (2003). References 38 and 39 report the discovery of sterotypical expression waves during the Plasmodium spp. division cycle.

    PubMed  PubMed Central  Google Scholar 

  40. Gaji, R. Y., Behnke, M. S., Lehmann, M. M., White, M. W. & Carruthers, V. B. Cell cycle-dependent, intercellular transmission of Toxoplasma gondii is accompanied by marked changes in parasite gene expression. Mol. Microbiol. 79, 192–204 (2011).

    CAS  PubMed  Google Scholar 

  41. Behnke, M. S. et al. Coordinated progression through two subtranscriptomes underlies the tachyzoite cycle of Toxoplasma gondii. PLoS ONE 5, e12354 (2010). This paper shows that gene expression cascades occur during T. gondii development.

    PubMed  PubMed Central  Google Scholar 

  42. Riechmann, J. L. & Meyerowitz, E. M. The AP2/EREBP family of plant transcription factors. Biol. Chem. 379, 633–646 (1998).

    CAS  PubMed  Google Scholar 

  43. Radke, J. B. et al. ApiAP2 transcription factor restricts development of the Toxoplasma tissue cyst. Proc. Natl Acad. Sci. USA 110, 6871–6876 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Painter, H. J., Campbell, T. L. & Llinas, M. The Apicomplexan AP2 family: integral factors regulating Plasmodium development. Mol. Biochem. Parasitol. 176, 1–7 (2011).

    CAS  PubMed  Google Scholar 

  45. De Silva, E. K. et al. Specific DNA-binding by apicomplexan AP2 transcription factors. Proc. Natl Acad. Sci. USA 105, 8393–8398 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Suvorova, E. S. et al. Discovery of a splicing regulator required for cell cycle progression. PLoS Genet. 9, e1003305 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Doerig, C. et al. Signalling in malaria parasites. The MALSIG consortium. Parasite 16, 169–182 (2009).

    CAS  PubMed  Google Scholar 

  48. Ferguson, D. J. et al. MORN1 has a conserved role in asexual and sexual development across the apicomplexa. Eukaryot. Cell 7, 698–711 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Chen, C. T & Gubbels, M. J. The Toxoplasma gondii centrosome is the platform for internal daughter budding as revealed by a Nek1 kinase mutant. J. Cell Sci. 126, 3344–3355 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Reininger, L., Wilkes, J. M., Bourgade, H., Miranda-Saavedra, D. & Doerig, C. An essential Aurora-related kinase transiently associates with spindle pole bodies during Plasmodium falciparum erythrocytic schizogony. Mol. Microbiol. 79, 205–221 (2011). This study shows that cell cycle progression is asynchronous during P. falciparum schizogony.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Carvalho-Santos, Z. et al. Stepwise evolution of the centriole-assembly pathway. J. Cell Sci. 123, 1414–1426 (2010).

    CAS  PubMed  Google Scholar 

  52. Brooks, C. F. et al. Toxoplasma gondii sequesters centromeres to a specific nuclear region throughout the cell cycle. Proc. Natl Acad. Sci. USA 108, 3767–3772 (2011). This paper was the first to show that centromeres are clustered in Apicomplexa.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Hoeijmakers, W. A. et al. Plasmodium falciparum centromeres display a unique epigenetic makeup and cluster prior to and during schizogony. Cell. Microbiol. 14, 1391–1401 (2012).

    CAS  PubMed  Google Scholar 

  54. Kelly, J. M., McRobert, L. & Baker, D. A. Evidence on the chromosomal location of centromeric DNA in Plasmodium falciparum from etoposide-mediated topoisomerase-II cleavage. Proc. Natl Acad. Sci. USA 103, 6706–6711 (2006). This paper is the first biochemical identification of a P. falciparum centromere.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Iwanaga, S. et al. Functional identification of the Plasmodium centromere and generation of a Plasmodium artificial chromosome. Cell Host Microbe 7, 245–255 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Petter, M. et al. H2A.Z and H2B.Z double-variant nucleosomes define intergenic regions and dynamically occupy var gene promoters in the malaria parasite Plasmodium falciparum. Mol. Microbiol. 87, 1167–1182 (2013).

    CAS  PubMed  Google Scholar 

  57. Bartfai, R. et al. H2A.Z demarcates intergenic regions of the Plasmodium falciparum epigenome that are dynamically marked by H3K9ac and H3K4me3. PLoS Pathog. 6, e1001223 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Dalmasso, M. C., Onyango, D. O., Naguleswaran, A., Sullivan, W. J. Jr & Angel, S. O. Toxoplasma H2A variants reveal novel insights into nucleosome composition and functions for this histone family. J. Mol. Biol. 392, 33–47 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Lopez-Rubio, J. J., Mancio-Silva, L. & Scherf, A. Genome-wide analysis of heterochromatin associates clonally variant gene regulation with perinuclear repressive centers in malaria parasites. Cell Host Microbe 5, 179–190 (2009).

    CAS  PubMed  Google Scholar 

  60. Choi, S. W., Keyes, M. K. & Horrocks, P. LC/ESI-MS demonstrates the absence of 5-methyl-2′-deoxycytosine in Plasmodium falciparum genomic DNA. Mol. Biochem. Parasitol. 150, 350–352 (2006).

    CAS  PubMed  Google Scholar 

  61. Baum, J. et al. Molecular genetics and comparative genomics reveal RNAi is not functional in malaria parasites. Nucleic Acids Res. 37, 3788–3798 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Dalmasso, M. C., Sullivan, W. J. Jr & Angel, S. O. Canonical and variant histones of protozoan parasites. Front. Biosci. 16, 2086–2105 (2011).

    CAS  Google Scholar 

  63. Gissot, M. et al. Toxoplasma gondii chromodomain protein 1 binds to heterochromatin and colocalises with centromeres and telomeres at the nuclear periphery. PLoS ONE 7, e32671 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Kumar, S. V. & Wigge, P. A. H2A.Z-containing nucleosomes mediate the thermosensory response in Arabidopsis. Cell 140, 136–147 (2010).

    CAS  PubMed  Google Scholar 

  65. Flueck, C. et al. Plasmodium falciparum heterochromatin protein 1 marks genomic loci linked to phenotypic variation of exported virulence factors. PLoS Pathog. 5, e1000569 (2009).

    PubMed  PubMed Central  Google Scholar 

  66. Duraisingh, M. T. et al. Heterochromatin silencing and locus repositioning linked to regulation of virulence genes in Plasmodium falciparum. Cell 121, 13–24 (2005).

    CAS  PubMed  Google Scholar 

  67. del Cacho, E. et al. Meiotic chromosome pairing and bouquet formation during Eimeria tenella sporulation. Int. J. Parasitol. 40, 453–462 (2010).

    CAS  PubMed  Google Scholar 

  68. Hinterberg, K., Mattei, D., Wellems, T. E. & Scherf, A. Interchromosomal exchange of a large subtelomeric segment in a Plasmodium falciparum cross. EMBO J. 13, 4174–4180 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Freitas-Junior, L. H. et al. Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum. Nature 407, 1018–1022 (2000).

    CAS  PubMed  Google Scholar 

  70. Volz, J. et al. Potential epigenetic regulatory proteins localise to distinct nuclear sub-compartments in Plasmodium falciparum. Int. J. Parasitol. 40, 109–121 (2010).

    CAS  PubMed  Google Scholar 

  71. Oehring, S. C. et al. Organellar proteomics reveals hundreds of novel nuclear proteins in the malaria parasite Plasmodium falciparum. Genome Biol. 13, R108 (2012).

    PubMed  PubMed Central  Google Scholar 

  72. Suvorova, E. S., Lehmann, M. M., Kratzer, S. & White, M. W. Nuclear actin-related protein is required for chromosome segregation in Toxoplasma gondii. Mol. Biochem. Parasitol. 181, 7–16 (2012).

    CAS  PubMed  Google Scholar 

  73. Weiner, A. et al. 3D nuclear architecture reveals coupled cell cycle dynamics of chromatin and nuclear pores in the malaria parasite Plasmodium falciparum. Cell. Microbiol. 13, 967–977 (2011). This paper reports the first observation of nuclear-pore dynamics in P. falciparum.

    CAS  PubMed  Google Scholar 

  74. Russell, D. G. & Burns, R. G. The polar ring of coccidian sporozoites: a unique microtubule-organizing centre. J. Cell Sci. 65, 193–207 (1984).

    CAS  PubMed  Google Scholar 

  75. Aikawa, M. The fine structure of the erythrocytic stages of three avian malarial parasites, Plasmodium fallax, P. lophurae, and P. cathemerium. Am. J. Trop. Med. Hyg. 15, 449–471 (1966).

    CAS  PubMed  Google Scholar 

  76. D'Haese, J., Mehlhorn, H. & Peters, W. Comparative electron microscope study of pellicular structures in coccidia (Sarcocystis, Besnoitia and Eimeria). Int. J. Parasitol. 7, 505–518 (1977).

    CAS  PubMed  Google Scholar 

  77. Dubremetz, J. F. & Torpier, G. Freeze fracture study of the pellicle of an eimerian sporozoite (Protozoa, Coccidia). J. Ultrastruct. Res. 62, 94–109 (1978).

    CAS  PubMed  Google Scholar 

  78. Tran, J. Q. et al. RNG1 is a late marker of the apical polar ring in Toxoplasma gondii. Cytoskeleton (Hoboken) 67, 586–598 (2010).

    CAS  Google Scholar 

  79. Gould, S. B. et al. Ciliate pellicular proteome identifies novel protein families with characteristic repeat motifs that are common to alveolates. Mol. Biol. Evol. 28, 1319–1331 (2011). This paper uses a comparative proteomic study to discover shared elements of cellular architecture.

    CAS  PubMed  Google Scholar 

  80. Hu, K., Roos, D. S. & Murray, J. M. A novel polymer of tubulin forms the conoid of Toxoplasma gondii. J. Cell Biol. 156, 1039–1050 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Hu, K. et al. Cytoskeletal components of an invasion machine — the apical complex of Toxoplasma gondii. PLoS Pathog. 2, e13 (2006).

    PubMed  PubMed Central  Google Scholar 

  82. Francia, M. E. et al. Cell division in apicomplexan parasites is organized by a homolog of the striated rootlet fiber of algal flagella. PLoS Biol. 10, e1001444 (2012). This study shows the algal ancestry of cell division structures in T. gondii.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Lechtreck, K. F. Analysis of striated fiber formation by recombinant SF-assemblin in vitro. J. Mol. Biol. 279, 423–438 (1998).

    CAS  PubMed  Google Scholar 

  84. Mann, T. & Beckers, C. Characterization of the subpellicular network, a filamentous membrane skeletal component in the parasite Toxoplasma gondii. Mol. Biochem. Parasitol. 115, 257–268 (2001).

    CAS  PubMed  Google Scholar 

  85. Morrissette, N. S., Murray, J. M. & Roos, D. S. Subpellicular microtubules associate with an intramembranous particle lattice in the protozoan parasite Toxoplasma gondii. J. Cell Sci. 110, 35–42 (1997).

    CAS  PubMed  Google Scholar 

  86. Anderson-White, B. et al. Cytoskeleton assembly in Toxoplasma gondii cell division. Int. Rev. Cell. Mol. Biol. 298, 1–31 (2012). This paper gives a comprehensive review of T. gondii cytoskeletal structures and stepwise daughter cell assembly.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Gaskins, E. et al. Identification of the membrane receptor of a class XIV myosin in Toxoplasma gondii. J. Cell Biol. 165, 383–393 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Keeley, A. & Soldati, D. The glideosome: a molecular machine powering motility and host-cell invasion by Apicomplexa. Trends Cell Biol. 14, 528–532 (2004).

    CAS  PubMed  Google Scholar 

  89. Kudryashev, M. et al. Positioning of large organelles by a membrane-associated cytoskeleton in Plasmodium sporozoites. Cell. Microbiol. 12, 362–371 (2010).

    CAS  PubMed  Google Scholar 

  90. Gould, S. B., Tham, W. H., Cowman, A. F., McFadden, G. I. & Waller, R. F. Alveolins, a new family of cortical proteins that define the protist infrakingdom Alveolata. Mol. Biol. Evol. 25, 1219–1230 (2008).

    CAS  PubMed  Google Scholar 

  91. Leander, B. S., Kuvardina, O. N., Aleshin, V. V., Mylnikov, A. P. & Keeling, P. J. Molecular phylogeny and surface morphology of Colpodella edax (Alveolata): insights into the phagotrophic ancestry of apicomplexans. J. Eukaryot. Microbiol. 50, 334–340 (2003).

    PubMed  Google Scholar 

  92. Khater, E. I., Sinden, R. E. & Dessens, J. T. A malaria membrane skeletal protein is essential for normal morphogenesis, motility, and infectivity of sporozoites. J. Cell Biol. 167, 425–432 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Tremp, A. Z., Khater, E. I. & Dessens, J. T. IMC1b is a putative membrane skeleton protein involved in cell shape, mechanical strength, motility, and infectivity of malaria ookinetes. J. Biol. Chem. 283, 27604–27611 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Tremp, A. Z. & Dessens, J. T. Malaria IMC1 membrane skeleton proteins operate autonomously and participate in motility independently of cell shape. J. Biol. Chem. 286, 5383–5391 (2011).

    CAS  PubMed  Google Scholar 

  95. Anderson-White, B. R. et al. A family of intermediate filament-like proteins is sequentially assembled into the cytoskeleton of Toxoplasma gondii. Cell. Microbiol. 13, 18–31 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Morrissette, N. S. & Sibley, L. D. Disruption of microtubules uncouples budding and nuclear division in Toxoplasma gondii. J. Cell Sci. 115, 1017–1025 (2002).

    CAS  PubMed  Google Scholar 

  97. Beck, J. R. et al. A novel family of Toxoplasma IMC proteins displays a hierarchical organization and functions in coordinating parasite division. PLoS Pathog. 6, e1001094 (2010).

    PubMed  PubMed Central  Google Scholar 

  98. Fung, C., Beck, J. R., Robertson, S. D., Gubbels, M. J. & Bradley, P. J. Toxoplasma ISP4 is a central IMC sub-compartment protein whose localization depends on palmitoylation but not myristoylation. Mol. Biochem. Parasitol. 184, 99–108 (2012). This paper is the first to identify IMC subcompartment proteins.

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Mann, T., Gaskins, E. & Beckers, C. Proteolytic processing of TgIMC1 during maturation of the membrane skeleton of Toxoplasma gondii. J. Biol. Chem. 277, 41240–41246 (2002).

    CAS  PubMed  Google Scholar 

  100. Gubbels, M. J., Wieffer, M. & Striepen, B. Fluorescent protein tagging in Toxoplasma gondii: identification of a novel inner membrane complex component conserved among Apicomplexa. Mol. Biochem. Parasitol. 137, 99–110 (2004).

    CAS  PubMed  Google Scholar 

  101. De Napoli, M. G. et al. N-terminal palmitoylation is required for Toxoplasma gondii HSP20 inner membrane complex localization. Biochim. Biophys. Acta 1833, 1329–1337 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Frenal, K. et al. Global analysis of apicomplexan protein S-acyl transferases reveals an enzyme essential for invasion. Traffic 14, 895–911 (2013). This paper reports the localization of all S-acyl-transferases that are encoded by the genomes of T. gondii and P. falciparum.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Hu, K. Organizational changes of the daughter basal complex during the parasite replication of Toxoplasma gondii. PLoS Pathog. 4, e10 (2008).

    PubMed  PubMed Central  Google Scholar 

  104. Lorestani, A. et al. A Toxoplasma MORN1 null mutant undergoes repeated divisions but is defective in basal assembly, apicoplast division and cytokinesis. PLoS ONE 5, e12302 (2010).

    PubMed  PubMed Central  Google Scholar 

  105. Gubbels, M. J., Vaishnava, S., Boot, N., Dubremetz, J. F. & Striepen, B. A. MORN-repeat protein is a dynamic component of the Toxoplasma gondii cell division apparatus. J. Cell Sci. 119, 2236–2245 (2006).

    CAS  PubMed  Google Scholar 

  106. Hu, K. et al. Daughter cell assembly in the protozoan parasite Toxoplasma gondii. Mol. Biol. Cell 13, 593–606 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Heaslip, A. T., Dzierszinski, F., Stein, B. & Hu, K. TgMORN1 is a key organizer for the basal complex of Toxoplasma gondii. PLoS Pathog. 6, e1000754 (2010).

    PubMed  PubMed Central  Google Scholar 

  108. Carruthers, V. & Boothroyd, J. C. Pulling together: an integrated model of Toxoplasma cell invasion. Curr. Opin. Microbiol. 10, 83–89 (2007).

    CAS  PubMed  Google Scholar 

  109. Ogino, N. & Yoneda, C. The fine structure and mode of division of Toxoplasma gondii. Arch. Ophthalmol. 75, 218–227 (1966).

    CAS  PubMed  Google Scholar 

  110. Bannister, L. H., Hopkins, J. M., Fowler, R. E., Krishna, S. & Mitchell, G. H. Ultrastructure of rhoptry development in Plasmodium falciparum erythrocytic schizonts. Parasitology 121, 273–287 (2000).

    PubMed  Google Scholar 

  111. Shaw, M. K., Roos, D. S. & Tilney, L. G. Acidic compartments and rhoptry formation in Toxoplasma gondii. Parasitology 117, 435–443 (1998).

    CAS  PubMed  Google Scholar 

  112. Soldati, D., Dubremetz, J. F. & Lebrun, M. Microneme proteins: structural and functional requirements to promote adhesion and invasion by the apicomplexan parasite Toxoplasma gondii. Int. J. Parasitol. 31, 1293–1302 (2001).

    CAS  PubMed  Google Scholar 

  113. Hager, K. M., Striepen, B., Tilney, L. G. & Roos, D. S. The nuclear envelope serves as an intermediary between the ER and Golgi complex in the intracellular parasite Toxoplasma gondii. J. Cell Sci. 112, 2631–2638 (1999).

    CAS  PubMed  Google Scholar 

  114. Hartmann, J. et al. Golgi and centrosome cycles in Toxoplasma gondii. Mol. Biochem. Parasitol. 145, 125–127 (2006).

    CAS  PubMed  Google Scholar 

  115. Agop-Nersesian, C. et al. Biogenesis of the inner membrane complex is dependent on vesicular transport by the alveolate specific GTPase Rab11B. PLoS Pathog. 6, e1001029 (2010).

    PubMed  PubMed Central  Google Scholar 

  116. Heaslip, A. T., Ems-McClung, S. C. & Hu, K. TgICMAP1 is a novel microtubule binding protein in Toxoplasma gondii. PLoS ONE 4, e7406 (2009).

    PubMed  PubMed Central  Google Scholar 

  117. Kremer, K. et al. An overexpression screen of Toxoplasma gondii Rab-GTPases reveals distinct transport routes to the micronemes. PLoS Pathog. 9, e1003213 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Schrevel, J. et al. Vesicle trafficking during sporozoite development in Plasmodium berghei: ultrastructural evidence for a novel trafficking mechanism. Parasitology 135, 1–12 (2008). This paper suggests that the striated fibre has a role in protein secretion.

    CAS  PubMed  Google Scholar 

  119. Mueller, C. et al. The Toxoplasma protein ARO mediates the apical positioning of rhoptry organelles, a prerequisite for host cell invasion. Cell Host Microbe 13, 289–301 (2013).

    CAS  PubMed  Google Scholar 

  120. Beck, J. R. et al. A Toxoplasma palmitoyl acyl transferase and the palmitoylated armadillo repeat protein TgARO govern apical rhoptry tethering and reveal a critical role for the rhoptries in host cell invasion but not egress. PLoS Pathog. 9, e1003162 (2013). References 119 and 120 report that compartment-specific palmitoylation is required for protein localization to a cellular subcompartment in T. gondii.

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Van Dooren, G. G. & Striepen, B. The algal past and parasite present of the apicoplast. Annu. Rev. Microbiol. 67, 271–289 (2013).

    CAS  PubMed  Google Scholar 

  122. Reiff, S. B., Vaishnava, S. & Striepen, B. The HU protein is important for apicoplast genome maintenance and inheritance in Toxoplasma gondii. Eukaryot. Cell 11, 905–915 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Seow, F. et al. The plastidic DNA replication enzyme complex of Plasmodium falciparum. Mol. Biochem. Parasitol. 141, 145–153 (2005).

    CAS  PubMed  Google Scholar 

  124. Dar, M. A., Sharma, A., Mondal, N. & Dhar, S. K. Molecular cloning of apicoplast-targeted Plasmodium falciparum DNA gyrase genes: unique intrinsic ATPase activity and ATP-independent dimerization of PfGyrB subunit. Eukaryot. Cell 6, 398–412 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Striepen, B. et al. The plastid of Toxoplasma gondii is divided by association with the centrosomes. J. Cell Biol. 151, 1423–1434 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  126. van Dooren, G. G. et al. Development of the endoplasmic reticulum, mitochondrion and apicoplast during the asexual life cycle of Plasmodium falciparum. Mol. Microbiol. 57, 405–419 (2005).

    CAS  PubMed  Google Scholar 

  127. Stanway, R. R. et al. Organelle segregation into Plasmodium liver stage merozoites. Cell. Microbiol. 13, 1768–1782 (2011).

    CAS  PubMed  Google Scholar 

  128. van Dooren, G. G. et al. A novel dynamin-related protein has been recruited for apicoplast fission in Toxoplasma gondii. Curr. Biol. 19, 267–276 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Gluenz, E., Povelones, M. L., Englund, P. T. & Gull, K. The kinetoplast duplication cycle in Trypanosoma brucei is orchestrated by cytoskeleton-mediated cell morphogenesis. Mol. Cell. Biol. 31, 1012–1021 (2011).

    CAS  PubMed  Google Scholar 

  130. Robinson, D. R. & Gull, K. Basal body movements as a mechanism for mitochondrial genome segregation in the trypanosome cell cycle. Nature 352, 731–733 (1991).

    CAS  PubMed  Google Scholar 

  131. He, C. Y. Golgi biogenesis in simple eukaryotes. Cell. Microbiol. 9, 566–572 (2007).

    CAS  PubMed  Google Scholar 

  132. Pino, P. et al. A tetracycline-repressible transactivator system to study essential genes in malaria parasites. Cell Host Microbe 12, 824–834 (2012). This paper reports a conditional mutagenesis strategy that is based on the use of a tetracycline repressible promoter, for generating mutants in P. falciparum.

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Collins, C. R. et al. Robust inducible Cre recombinase activity in the human malaria parasite Plasmodium falciparum enables efficient gene deletion within a single asexual erythrocytic growth cycle. Mol. Microbiol. 88, 687–701 (2013). This paper reports a conditional mutagenesis strategy that is based on the use of the Cre recombinase, for generating mutants in P. falciparum.

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank M. White and J.-F. Dubremetz for many discussions. This work is supported by grants from the US National Institutes of Health to B.S. and M. White, M.E.F was supported by an EMBO short-term fellowship, and B.S. is a Georgia Research Alliance distinguished investigator.

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Authors and Affiliations

  1. Department of Cellular Biology, University of Georgia, Athens, 30602, Georgia, USA

    Maria E. Francia & Boris Striepen

  2. Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, 30602, Georgia, USA

    Boris Striepen

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  1. Maria E. Francia
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Correspondence to Boris Striepen.

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Glossary

Apicomplexa

A phylum of single-celled eukaryotic pathogens that are related to dinoflagellates and ciliates.

Centrosome

The microtubule organizing centre of the mitotic spindle. It can contain a pair of centrioles as well as pericentriolar material.

Centromeres

The typically single locations on chromosomes where the kinetochore assembles. The kinetochore is the point of attachment for microtubules during mitosis. Centromeres are marked by the presence of a variant histone H3, known as CenH3 or CenPA.

Telomeres

The ends of linear chromosomes. They commonly consist of repetitive DNA and show chromatin modification that is associated with silencing.

Endodyogeny

The mode of replication that is used by Toxoplasma gondii. DNA replication is immediately followed by nuclear division and budding.

Schizogony

The mode of replication of Plasmodium falciparum. Multiple rounds of mitosis yield a multinucleated syncytium, which is followed by synchronous budding.

Endopolygeny

The mode of replication that is used by Sarcocystis neurona. Multiple rounds of mitosis without nuclear division, leading to a polyploid nucleus. Nuclear division coincides with budding.

Syncytium

A multinucleated cell that results from multiple rounds of mitosis in the absence of cytokinesis.

Striated fibre

A fibre that is formed by the polymerization of striated fibre assemblin (SFA) proteins. It organizes the flagellar rootlet in single-celled algae and budding in apicomplexan parasites.

Inner membrane complex

(IMC). A system of flattened membrane cisternae that underlie the plasma membrane of alveolates (ciliates, dinoflagellates and apicomplexans).

Acylation

A post-translational addition of a palmytoyl or myristoyl moiety. This is catalysed by an acyl-transferase, which controls the affinity of a protein for lipid membranes.

Dense granules

Secretory organelles of Apicomplexa that function in host cell modification.

Rhoptries and micronemes

Secretory organelles of apicomplexan parasites that function in motility and invasion.

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Francia, M., Striepen, B. Cell division in apicomplexan parasites. Nat Rev Microbiol 12, 125–136 (2014). https://doi.org/10.1038/nrmicro3184

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