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  • Review Article
  • Published:

Gliding motility powers invasion and egress in Apicomplexa

Key Points

  • Apicomplexa are unicellular eukaryotic parasites that exhibit two types of secretory organelle at their apical pole and a membranous system that underlies their plasma membrane.

  • Apicomplexa are obligate intracellular parasites that use a substrate-dependent gliding motility to move and to actively enter host cells, and to egress from the infected cells.

  • Motility by Apicomplexa relies on the translocation of parasite surface adhesins from the apical pole, from where they are secreted to the posterior pole in a process powered by a machinery termed the glideosome. The rearward translocation of the adhesins bound to host cell receptors involves the actomyosin system, which propels the parasite forward.

  • The invasion of host cells involves the formation of a moving junction at the point of apposition between the plasma membrane of the parasite and the host cell. Both ligands and receptors are secreted by the parasite, and they form a solid platform to support the force applied by the parasite during penetration.

  • A tightly regulated signalling cascade coordinates the apical secretion of microneme proteins and the activation of the glideosome, which leads to gliding motility.

Abstract

Protozoan parasites have developed elaborate motility systems that facilitate infection and dissemination. For example, amoebae use actin-rich membrane extensions called pseudopodia, whereas Kinetoplastida are propelled by microtubule-containing flagella. By contrast, the motile and invasive stages of the Apicomplexa — a phylum that contains the important human pathogens Plasmodium falciparum (which causes malaria) and Toxoplasma gondii (which causes toxoplasmosis) — have a unique machinery called the glideosome, which is composed of an actomyosin system that underlies the plasma membrane. The glideosome promotes substrate-dependent gliding motility, which powers migration across biological barriers, as well as active host cell entry and egress from infected cells. In this Review, we discuss the discovery of the principles that govern gliding motility, the characterization of the molecular machinery involved, and its impact on parasite invasion and egress from infected cells.

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Figure 1: The life cycles of Toxoplasma gondii and Plasmodium falciparum.
Figure 2: Major developments in the history of the capping model.
Figure 3: Gliding motility in Apicomplexa.
Figure 4: Gliding motility is initiated at the apical pole and depends on the glideosome complex.
Figure 5: Motility drives egress and invasion.

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Acknowledgements

The authors thank H. Bullen and D. Jacot for critical reading of the manuscript. They are grateful to M. Blackman and J. Thomas, and to F. Frischknecht and M. Brochet, for providing the movies of merozoite egress and invasion, and of sporozoite and ookinete motility, respectively. During the manuscript revision process, 25% of the text and references had to be removed owing to space constraints. The authors apologize that not all relevant studies could not be discussed and cited as a result of this. K.F. is supported by the Swiss National Foundation (FN3100A0-116722) and received funding from the Sir Jules Thorn Charitable Overseas Trust reg., Schaan subsidy for young researchers. M.L. received funding from the Laboratoire d'Excellence (LabEx; ParaFrap ANR-11-LABX-0024). D.S.-F. is an advanced international scholar of the Howard Hughes Medical Institute.

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Authors and Affiliations

Authors

Contributions

D.S-F., K.F., J-F.D. and M.L. all contributed to the writing of this Review, and D.S-F., K.F. and M.L. worked on the review and editing of the manuscript before submission.

Corresponding authors

Correspondence to Karine Frénal or Dominique Soldati-Favre.

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The authors declare no competing financial interests.

Supplementary information

Supplementary information S6 (table)

Summary of proteins functionally shown to be involved in apicomplexan motility, invasion or egress (DOC 378 kb)

Supplementary Movie S1

Circular gliding of Plasmodium berghei sporozoite. Movie courtesy of F. Frischknecht, Centre for Infectious Diseases, Heidelberg University Hospital, Germany. (AVI 490 kb)

Supplementary Movie S2

Circular gliding of Toxoplasma gondii tachyzoite (AVI 317 kb)

Supplementary Movie S3

Helical gliding of Toxoplasma gondii tachyzoite (AVI 811 kb)

Supplementary Movie S4

Stationary twirling of Toxoplasma gondii tachyzoite (AVI 507 kb)

Supplementary Movie S5

Gliding of Plasmodium berghei ookinetes. Movie courtesy of M. Brochet, Faculty of Medicine, University of Geneva, Switzerland. (AVI 809 kb)

Supplementary Movie S7

Egress and invasion of Plasmodium falciparum merozoites. Movie courtesy of M. Blackman and J. Thomas, The Francis Crick Institute, London, United Kingdom. (MOV 174 kb)

PowerPoint slides

Glossary

Apicomplexa

A phylum of diverse, single-celled, eukaryotic, obligate intracellular parasites.

Alveolata

A group of protists within the kingdom Eukarya that contains the phyla Dinoflagellata, Ciliophora and Apicomplexa.

Toxoplasmosis

A food-borne infection caused by the parasite Toxoplasma gondii. The infection is usually mild or even asymptomatic, but can have serious consequences in patients who are immunocompromised and for the fetus in the case of primary infection during pregnancy.

Sporozoites

The infectious and motile stage produced in oocysts and transmitted by the definitive host.

Tachyzoites

The motile and fast-replicative stage of Toxoplasma gondii that is able to invade any nucleated cell in the host.

Merozoites

The stage of Plasmodium spp. that infects erythrocytes, in which it initiates a new asexual life cycle.

Actomyosin system

A complex that comprises actin filaments, myosin and associated proteins, and that is involved in movement.

Glideosome

A molecular complex that powers gliding motility in apicomplexan parasites.

Circumsporozoite precipitation reaction

A reaction in which sporozoites, incubated in immune serum, eject a tail-like precipitate in a process that corresponds to the shedding of the glycosylphosphatidylinositol-anchored circumsporozoite protein crosslinked by antibodies.

Cytochalasin

A type of fungal metabolite that inhibits actin polymerization. Cytochalasin A and cytochalasin B can have pleiotropic effects, which include the inhibition of monosaccharide uptake and transport.

Coccidia

A subclass of Apicomplexa comprising parasites that infect the intestinal tracts of animals, such as Toxoplasma gondii, Neospora spp., Eimeria spp. and Sarcocystis spp. These parasites harbour an apical structure, termed a conoid, that consists of anticlockwise spiralling fibres.

Gregarina

Large apicomplexan parasites that are 0.5 mm in size and are capable of infecting terrestrial and marine invertebrates.

Moving junction

An intimate junction made at the point of apposition between the parasite and host cell plasma membranes. It is also referred to as a tight junction or circular junction in the literature.

Pellicle

In apicomplexans, the three-layered structure comprising the plasma membrane and the underlying inner membrane complex.

Inner membrane complex

(IMC). In apicomplexans, one or more flattened vesicular sacs, also named alveoli, that are visible as double-membranous structures underneath the plasma membrane. The IMC is composed of only one alveolus in Plasmodium spp. or of a patchwork of alveoli in Toxoplasma gondii or Eimeria spp.

Rhoptries

Club-shaped secretory organelles that are located at the apical pole of parasites and are composed of two subcompartments: the neck and the bulb.

Micronemes

Elliptic secretory organelles that are located at the apical pole of parasites.

Actin-binding proteins

(ABPs). Proteins that bind to globular and/or filamentous actin and influence, for example, monomer sequestration or delivery, filament nucleation, polymerization, depolarization, stability and capping.

Myosin

A molecular motor that binds to cargo and converts chemical energy released by ATP hydrolysis into directed movement along tracks of actin filaments.

Acylation

The co-translational or post-translational addition of a lipid onto protein residues; examples include myristoylation (in which a 14-carbon saturated fatty acid is added onto a glycine residue at position 2) and palmitoylation (in which a 16-carbon saturated fatty acid is added onto a cysteine residue).

Conoid

A cone-shaped, apical structure that is present in coccidian parasites and is made of spirally arranged tubulin fibres. The conoid protrudes in a calcium-dependent manner during motility, invasion and egress.

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Frénal, K., Dubremetz, JF., Lebrun, M. et al. Gliding motility powers invasion and egress in Apicomplexa. Nat Rev Microbiol 15, 645–660 (2017). https://doi.org/10.1038/nrmicro.2017.86

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