Actin/Myosin-Based Gliding Motility in Apicomplexan Parasites

  • Kai Matuschewski
  • Herwig Schüler
Part of the Subcellular Biochemistry book series (SCBI, volume 47)


Apicomplexan parasites move and actively enter host cells by substrate-dependent gliding motility, an unusual form of eukaryotic locomotion that differs fundamentally from the motility of prokaryotic and viral pathogens. Recent research has uncovered some of the cellular and molecular mechanisms underlying parasite motility, transmigration, and cell invasion during life cycle progression. The gliding motor machinery is embedded between the plasma membrane and the inner membrane complex, a unique double membrane layer. It consists of immobilized unconventional myosins, short actin stubs, and TRAP-family invasins. Assembly of this motor machinery enables force generation between parasite cytoskeletal components and an extracellular substratum. Unique properties of the individual components suggest that the rational design of motility inhibitors may lead to new intervention strategies to combat some of the most devastating human and livestock diseases.


Actin Polymer Toxoplasma Gondii Parasitophorous Vacuole Apicomplexan Parasite Host Cell Invasion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Fowler RE, Margos G, Mitchell GH. The cytoskeleton and motility in apicomplexan invasion. Adv Parasitol 2004; 56:213–263.PubMedCrossRefGoogle Scholar
  2. 2.
    Heintzelman MB. Cellular and molecular mechanics of gliding locomotion in eukaryotes. Int Rev Cytol 2006; 251:79–129.PubMedCrossRefGoogle Scholar
  3. 3.
    Kappe SH, Buscaglia CA, Bergman LW et al. Apicomplexan gliding motility and host cell invasion: Overhauling the motor model. Trends Parasitol 2004; 20(1):13–16.PubMedCrossRefGoogle Scholar
  4. 4.
    Sibley LD. Intracellular parasite invasion strategies. Science 2004; 304(5668):248–253.PubMedCrossRefGoogle Scholar
  5. 5.
    Vanderberg JP, Frevert U. Intravital microscopy demonstrating antibody-mediated immobilization of Plasmodium berghei sporozoites injected into skin by mosquitoes. Int J Parasitol 2004; 34(9):991–996.PubMedCrossRefGoogle Scholar
  6. 6.
    Amino R, Thiberge S, Martin B et al. Quantitative imaging of Plasmodium transmission from mosquito to mammal. Nat Med 2006; 12:220–224.PubMedCrossRefGoogle Scholar
  7. 7.
    Frevert U, Engelmann S, Zougbédé S et al. Intravital observation of Plasmodium berghei sporozoite infection of the liver. PLoS Biol 2005; 3(6):el92.CrossRefGoogle Scholar
  8. 8.
    Barragan A, Sibley LD. Transepithelial migration of Toxoplasma gondii is linked to parasite motility and virulence. J Exp Med 2002; 195(12):1625–1633.PubMedCrossRefGoogle Scholar
  9. 9.
    Barragan A, Sibley LD. Migration of Toxoplasma gondii across biological barriers. Trends Microbiol 2003; 11(9):426–430.PubMedCrossRefGoogle Scholar
  10. 10.
    Carruthers VB, Sibley LD. Sequential protein secretion from three distinct organelles of Toxoplasma gondii accompanies invasion of human fibroblasts. Eur J Cell Biol 1997; 73(2):114–123.PubMedGoogle Scholar
  11. 11.
    Small JV, Resch GP. The comings and goings of actin: Coupling protrusion and retraction in cell motility. Curr Opin Cell Biol 2005; 17(5):517–523.PubMedCrossRefGoogle Scholar
  12. 12.
    Bray D. Cell movements: From molecules to motility. 2nd ed. New York: Garland Publishing, 2000.Google Scholar
  13. 13.
    Russell DG, Sinden RE. The role of the cytoskeleton in the motility of coccidian sporozoites. J Cell Sci 1981; 50:345–359.PubMedGoogle Scholar
  14. 14.
    King CA. Cell motility of sporozoan protozoa. Parasitol Today 1988; 4(11):315–319.PubMedCrossRefGoogle Scholar
  15. 15.
    Vanderberg JP. Studies on the motility of Plasmodium sporozoites. J Protozool 1974; 21(4):527–537.PubMedGoogle Scholar
  16. 16.
    Vanderberg JP. Development of infectivity by the Plasmodium berghei sporozoite. J Parasitol 1975; 61(1):43–50.PubMedCrossRefGoogle Scholar
  17. 17.
    Frischknecht F, Baldacci P, Martin B et al. Imaging movement of malaria parasites during transmission by Anopheles mosquitoes. Cell Microbiol 2004; 6(7):687–694.PubMedCrossRefGoogle Scholar
  18. 18.
    Håkansson S, Morisaki H, Heuser J et al. Time-lapse video microscopy of gliding motility in Toxoplasma gondii reveals a novel, biphasic mechanism of cell locomotion. Mol Biol Cell 1999; 10(11):3539–3547.PubMedGoogle Scholar
  19. 19.
    Vlachou D, Zimmermann T, Cantera R et al. Real-time, in vivo analysis of malaria ookinete locomotion and mosquito midgut invasion. Cell Microbiol 2004; 6(7):671–685.PubMedCrossRefGoogle Scholar
  20. 20.
    Vanderberg JP, Chew S, Stewart MJ. Plasmodium sporozoite interactions with macrophages in vitro: A videomicroscopic analysis. J Protozool 1990; 37(6):528–536.PubMedGoogle Scholar
  21. 21.
    Mota MM, Pradel G, Vanderberg JP et al. Migration of Plasmodium sporozoites through cells before infection. Science 2001; 291(5501):l4l–l44.CrossRefGoogle Scholar
  22. 22.
    Carruthers V, Boothroyd JC. Pulling together: An integrated model of Toxoplasma cell invasion. Curr Opin Microbiol 2006; 9:1–7.CrossRefGoogle Scholar
  23. 23.
    Morrissette NS, Sibley LD. Cytoskeleton of apicomplexan parasites. Microbiol Mol Biol Rev 2002; 66(1):21–38.PubMedCrossRefGoogle Scholar
  24. 24.
    Mann T, Beckers C. Characterization of the subpellicular network, a filamentous membrane skeletal component in the parasite Toxoplasma gondii. Mol Biochem Parasitol 2001; 115(2):257–268.PubMedCrossRefGoogle Scholar
  25. 25.
    Morrissette NS, Murray JM, Roos DS. Subpellicular microtubules associate with an intramembranous particle lattice in the protozoan parasite Toxoplasma gondii. J Cell Sci 1997; 110 (Pt 1):35–42.PubMedGoogle Scholar
  26. 26.
    Hu K, Johnson J, Florens L et al. Cytoskeletal components of an invasion machine-the apical complex of Toxoplasma gondii. PLoS Pathog 2006; 2(2):e13.PubMedCrossRefGoogle Scholar
  27. 27.
    Meissner M, Schlüter D, Soldati D. Role of Toxoplasma gondii myosin A in powering parasite gliding and host cell invasion. Science 2002; 298(5594):837–840.PubMedCrossRefGoogle Scholar
  28. 28.
    Heintzelman MB, Schwartzman JD. A novel class of unconventional myosins from Toxoplasma gondii. J Mol Biol 1997; 271(1):139–146.PubMedCrossRefGoogle Scholar
  29. 29.
    Foth BJ, Goedecke MC, Soldati D. New insights into myosin evolution and classification. Proc Natl Acad Sci USA 2006; 103(10):3681–3686.PubMedCrossRefGoogle Scholar
  30. 30.
    Herm-Götz A, Weiss S, Stratmann R et al. Toxoplasma gondii myosin A and its light chain: A fast, single-headed, plus-end-directed motor. EMBO J 2002; 21(9):2149–2158.PubMedCrossRefGoogle Scholar
  31. 31.
    Mermall V, Post PL, Mooseker MS. Unconventional myosins in cell movement, membrane traffic, and signal transduction. Science 1998; 279(5350):527–533.PubMedCrossRefGoogle Scholar
  32. 32.
    Gaskins E, Gilk S, DeVore N et al. Identification of the membrane receptor of a class XIV myosin in Toxoplasma gondii. J Cell Biol 2004; 165(3):383–393.PubMedCrossRefGoogle Scholar
  33. 33.
    Bergman LW, Kaiser K, Fujioka H et al. Myosin A tail domain interacting protein (MTIP) localizes to the inner membrane complex of Plasmodium sporozoites. J Cell Sci 2003; 116 (Pt 1):39–49.PubMedCrossRefGoogle Scholar
  34. 34.
    Baum J, Richard D, Healer J et al. A conserved molecular motor drives cell invasion and gliding motility across malaria life cycle stages and other apicomplexan parasites. J Biol Chem 2006; 281(8):5197–5208.PubMedCrossRefGoogle Scholar
  35. 35.
    Green JL, Martin SR, Fielden J et al. The MTIP-myosin A complex in blood stage malaria parasites. J Mol Biol 2006; 355(5):933–941.PubMedCrossRefGoogle Scholar
  36. 36.
    Jones ML, Kitson EL, Rayner JC. Plasmodium falciparum erythrocyte invasion: A conserved myosin associated complex. Mol Biochem Parasitol 2006; 147(1):74–84.PubMedCrossRefGoogle Scholar
  37. 37.
    Bosch J, Turley S, Daly TM et al. Structure of the MTIP-MyoA complex, a key component of the malaria parasite invasion motor. Proc Natl Acad Sci USA 2006; 103(13):4852–4857.PubMedCrossRefGoogle Scholar
  38. 38.
    Dobrowolski JM, Sibley LD. Toxoplasma invasion of mammalian cells is powered by the actin cytoskeleton of the parasite. Cell 1996; 84(6):933–939.PubMedCrossRefGoogle Scholar
  39. 39.
    Miller LH, Aikawa M, Johnson JG et al. Interaction between cytochalasin B-treated malarial parasites and erythrocytes: Attachment and junction formation. J Exp Med 1979; 149(1):172–184.PubMedCrossRefGoogle Scholar
  40. 40.
    Schatten H, Sibley LD, Ris H. Structural evidence for actin-like filaments in Toxoplasma gondii using high-resolution low-voltage field emission scanning electron microscopy. Microsc Microanal 2003; 9(4):330–335.PubMedCrossRefGoogle Scholar
  41. 41.
    Sahoo N, Beatty W, Heuser J et al. Unusual kinetic and structural properties control rapid assembly and turnover of actin in the parasite Toxoplasma gondii. Mol Biol Cell 2006; 17(2):895–906.PubMedCrossRefGoogle Scholar
  42. 42.
    Schmitz S, Grainger M, Howell S et al. Malaria parasite actin filaments are very short. J Mol Biol 2005; 349(1):113–125.PubMedCrossRefGoogle Scholar
  43. 43.
    Schüler H, Mueller AK, Matuschewski K. Unusual properties of Plasmodium falciparum actin: New insights into microfilament dynamics of apicomplexan parasites. FEBS Lett 2005; 579(3):655–660.PubMedCrossRefGoogle Scholar
  44. 44.
    Schüler H, Matuschewski K. Plasmodium motility: Actin not actin’ like actin. Trends Parasitol 2006; 22(4):146–147.PubMedCrossRefGoogle Scholar
  45. 45.
    Schüler H, Matuschewski K. Regulation of apicomplexan microfilament dynamics by a minimal set of actin-binding proteins. Traffic 2006; 7(11):1433–1439.PubMedCrossRefGoogle Scholar
  46. 46.
    Jewett TJ, Sibley LD. Aldolase forms a bridge between cell surface adhesins and the actin cytoskeleton in apicomplexan parasites. Mol Cell 2003; 11(4):885–894.PubMedCrossRefGoogle Scholar
  47. 47.
    Buscaglia CA, Coppens I, Hol WG et al. Sites of interaction between aldolase and thrombospondin-related anonymous protein in Plasmodium. Mol Biol Cell 2003; 14(12):4947–4957.PubMedCrossRefGoogle Scholar
  48. 48.
    Baum J, Papenfuss AT, Baum B et al. Regulation of apicomplexan actin-based motility. Nat Rev Microbiol 2006; 4(8):621–628.PubMedCrossRefGoogle Scholar
  49. 49.
    Schüler H, Mueller AK, Matuschewski K. A Plasmodium actin-depolymerizing factor that binds exclusively to actin monomers. Mol Biol Cell 2005; 16(9):4013–4023.PubMedCrossRefGoogle Scholar
  50. 50.
    Robson KJ, Hall JR, Jennings MW et al. A highly conserved amino-acid sequence in thrombospondin, properdin and in proteins from sporozoites and blood stages of a human malaria parasite. Nature 1988; 335(6185):79–82.PubMedCrossRefGoogle Scholar
  51. 51.
    Tomley FM, Soldati DS. Mix and match modules: Structure and function of microneme proteins in apicomplexan parasites. Trends Parasitol 2001; 17(2):81–88.PubMedCrossRefGoogle Scholar
  52. 52.
    Tucker RP. The thrombospondin type 1 repeat superfamily. Int J Biochem Cell Biol 2004; 36(6):969–974.PubMedCrossRefGoogle Scholar
  53. 53.
    Whittaker CA, Hynes RO. Distribution and evolution of von Willebrand/integrin A domains: Widely dispersed domains with roles in cell adhesion and elsewhere. Mol Biol Cell 2002; 13(10):3369–3387.PubMedCrossRefGoogle Scholar
  54. 54.
    Sultan AA, Thathy V, Frevert U et al. TRAP is necessary for gliding motility and infectivity of Plasmodium sporozoites. Cell 1997; 90(3):511–522.PubMedCrossRefGoogle Scholar
  55. 55.
    Kappe S, Bruderer T, Gantt S et al. Conservation of a gliding motility and cell invasion machinery in apicomplexan parasites. J Cell Biol 1999; 147(5):937–943.PubMedCrossRefGoogle Scholar
  56. 56.
    Matuschewski K, Nunes AC, Nussenzweig V et al. Plasmodium sporozoite invasion into insect and mammalian cells is directed by the same dual binding system. EMBO J 2002; 21(7):1597–1606.PubMedCrossRefGoogle Scholar
  57. 57.
    Rogers WO, Malik A, Mellouk S et al. Characterization of Plasmodium falciparum sporozoite surface protein 2. Proc Natl Acad Sci USA 1992; 89(19):9176–9180.PubMedCrossRefGoogle Scholar
  58. 58.
    Dessens JT, Beetsma AL, Dimopoulos G et al. CTRP is essential for mosquito infection by malaria ookinetes. EMBO J 1999; 18(22):6221–6227.PubMedCrossRefGoogle Scholar
  59. 59.
    Yuda M, Sakaida H, Chinzei Y. Targeted disruption of the Plasmodium berghei CTRP gene reveals its essential role in malaria infection of the vector mosquito. J Exp Med 1999; 190(11):1711–1716.PubMedCrossRefGoogle Scholar
  60. 60.
    Huynh MH, Carruthers VB. Toxoplasma MIC2 is a major determinant of invasion and virulence. PLoS Pathog 2006; 2(8):e84.PubMedCrossRefGoogle Scholar
  61. 61.
    Rabenau KE, Sohrabi A, Tripathy A et al. TgM2AP participates in Toxoplasma gondii invasion of host cells and is tightly associated with the adhesive protein TgMIC2. Mol Microbiol 2001; 41(3):537–547.PubMedCrossRefGoogle Scholar
  62. 62.
    Huynh MH, Rabenau KE, Harper JM et al. Rapid invasion of host cells by Toxoplasma requires secretion of the MIC2-M2AP adhesive protein complex. EMBO J 2003; 22(9):2082–2090.PubMedCrossRefGoogle Scholar
  63. 63.
    Stewart MJ, Vanderberg JP. Malaria sporozoites leave behind trails of circumsporozoite protein during gliding motility. J Protozool 1988; 35(3):389–393.PubMedGoogle Scholar
  64. 64.
    Carruthers VB, Giddings OK, Sibley LD. Secretion of micronemal proteins is associated with Toxoplasma invasion of host cells. Cell Microbiol 1999; 1(3):225–235.PubMedCrossRefGoogle Scholar
  65. 65.
    Kappes B, Doerig CD, Graeser R. An overview of Plasmodium protein kinases. Parasitol Today 1999; 15(11):449–454.PubMedCrossRefGoogle Scholar
  66. 66.
    Ishino T, Orito Y, Chinzei Y et al. A calcium-dependent protein kinase regulates Plasmodium ookinete access to the midgut epithelial cell. Mol Microbiol 2006; 59(4):1175–1184.PubMedCrossRefGoogle Scholar
  67. 67.
    Siden-Kiamos I, Ecker A, Nybäck S et al. Plasmodium berghei calcium-dependent protein kinase 3 is required for ookinete gliding motility and mosquito midgut invasion. Mol Microbiol 2006; 60(6):1355–1363.PubMedCrossRefGoogle Scholar
  68. 68.
    Carey KL, Westwood NJ, Mitchison TJ et al. A small-molecule approach to studying invasive mechanisms of Toxoplasma gondii. Proc Natl Acad Sci USA 2004; 101(19):7433–7438.PubMedCrossRefGoogle Scholar
  69. 69.
    Opitz C, Di Cristina M, Reiss M et al. Intramembrane cleavage of microneme proteins at the surface of the apicomplexan parasite Toxoplasma gondii. EMBO J 2002; 21(7):1577–1585.PubMedCrossRefGoogle Scholar
  70. 70.
    Zhou XW, Blackman MJ, Howell SA et al. Proteomic analysis of cleavage events reveals a dynamic two-step mechanism for proteolysis of a key parasite adhesive complex. Mol Cell Proteomics 2004; 3(6):565–576.PubMedCrossRefGoogle Scholar
  71. 71.
    Brossier F, Jewett TJ, Sibley LD et al. A spatially localized rhomboid protease cleaves cell surface adhesions essential for invasion by Toxoplasma. Proc Natl Acad Sci USA 2005; (11)102:4146–4151.CrossRefGoogle Scholar
  72. 72.
    Dowse TJ, Pascall JC, Brown KD et al. Apicomplexan rhomboids have a potential role in microneme protein cleavage during host cell invasion. Int J Parasitol 2005; 35(7):747–756.PubMedCrossRefGoogle Scholar
  73. 73.
    Dowse TJ, Soldati D. Rhomboid-like proteins in Apicomplexa: Phylogeny and nomenclature. Trends Parasitol 2005; 21(6):254–258.PubMedCrossRefGoogle Scholar
  74. 74.
    Baker RP, Wijetilaka R, Urban S. Two Plasmodium rhomboid proteases preferentially cleave different adhesions implicated in all invasive stages of malaria. PLoS Pathog 2006; 2(10):e113.PubMedCrossRefGoogle Scholar
  75. 75.
    Wetzel DM, Schmidt J, Kuhlenschmidt MS et al. Gliding motility leads to active cellular invasion by Cryptosporidium parvum sporozoites. Infect Immun 2005; 73(9):5379–5387.PubMedCrossRefGoogle Scholar
  76. 76.
    Spano F, Putignani L, Naitza S et al. Molecular cloning and expression analysis of a Cryptosporidium parvum gene encoding a new member of the thrombospondin family. Mol Biochem Parasitol 1998; 92(1):147–162.PubMedCrossRefGoogle Scholar
  77. 77.
    Khater EI, Sinden RE, Dessens JT. A malaria membrane skeletal protein is essential for normal morphogenesis, motility, and infectivity of sporozoites. J Cell Biol 2004; 167(3):425–432.PubMedCrossRefGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2008

Authors and Affiliations

  1. 1.Department of ParasitologyHeidelberg University School of MedicineHeidelbergGermany
  2. 2.Max Delbrück Center for Molecular MedicineBerlinGermany

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