Independent Roles of Apical Membrane Antigen 1 and Rhoptry Neck Proteins during Host Cell Invasion by Apicomplexa

Giovannini, Donatella; Späth, Stephan S.; Lacroix, Céline; Perazzi, Audrey; Bargieri, Daniel Youssef; Lagal, Vanessa; Lebugle, Camille; Combe, Audrey; Thiberge, Sabine; Baldacci, Patricia; Tardieux, Isabelle; Ménard, Robert

doi:10.1016/j.chom.2011.10.012

Cited by 109 publications

(183 citation statements)

References 42 publications

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“…In previous studies, AMA1, RON2, and RON4 were identified in sporozoites in addition to the merozoites [15,16]. In this study, we show that RON5 is also expressed in both merozoites and sporozoites.…”

Section: Discussionsupporting

confidence: 72%

“…Myc-tagged RON2 and AMA1 were shown to localize at the rhoptries and micronemes, respectively, in the rodent malaria parasite Plasmodum berghei merozoites and sporozoites [15]. These findings, taken together with the essentiality of RON4 in P. berghei sporozoite invasion of hepatocytes [16], suggest a role for RON proteins in both hepatocyte and erythrocyte invasion. This implies that Plasmodium parasites could employ similar invasion strategies in two distinct life cycle stages.…”

Section: Introductionmentioning

confidence: 99%

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Expression and localization of rhoptry neck protein 5 in merozoites and sporozoites of Plasmodium yoelii

Mutungi

Yahata

Sakaguchi

et al. 2014

Parasitology International

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Host cell invasion by Apicomplexan parasites marks a crucial step in disease establishment and pathogenesis. The moving junction (MJ) is a conserved and essential feature among parasites of this phylum during host cell invasion, thus proteins that associate at this MJ are potential targets of drug and vaccine development. In both Toxoplasma gondii and Plasmodium falciparum, a micronemal protein, Apical Membrane Antigen 1 (AMA1), and Rhoptry Neck proteins (RONs; RON2 and RON4) form an essential complex at the MJ. A new RON member, RON5, was shown to be important to stabilize RON2 during development and to associate with the MJ complex in T. gondii and also to be immunoprecipitated by anti-AMA1 antibody in P. falciparum. However, the detailed molecular nature of RON5 in Plasmodium is not well understood. In this study, Plasmodium yoelii RON5 gene (pyron5) was identified as an ortholog of P. falciparum and Plasmodium berghei ron5. The pyron5 exon-intron structure was validated by comparing genomic DNA sequences and experimentally determining fulllength complementary DNA sequence. PyRON5 was detected in water-insoluble fractions but no reliable transmembrane domain(s) were predicted by transmembrane prediction algorithms. PyRON5 formed a complex with PyRON4, PyRON2, and PyAMA1 in late schizont protein extract. Taken together, we infer that these results suggest that PyRON5 associates with membrane indirectly via other MJ components. Indirect immunofluorescence assay and immunoelectron microscopy localized PyRON5 at the rhoptry neck of the late schizont merozoites and at the rhoptry of sporozoites. The two-stage expression of PyRON5 suggests that PyRON5 plays roles in invasion of not only erythrocytes, but also of mosquito salivary glands and/or mammalian hepatocytes. Graphic Abstract Highlights• PyRON5 forms a complex with RON2, RON4, and AMA1 in schizont extract.• PyRON5, a putative soluble protein, exists in the water-insoluble fractions.• These suggest that PyRON5 associates with membrane via other complex component(s).• PyRON5 is expressed in the rhoptry in both merozoite and sporozoite parasites.• Targeting PyRON5 may prevent cell invasion by both merozoite and sporozoite. Mutungi et al., 2

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Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Expression and localization of rhoptry neck protein 5 in merozoites and sporozoites of Plasmodium yoelii

Mutungi

Yahata

Sakaguchi

et al. 2014

Parasitology International

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“…By normalizing the gDNA amount to the parasite tubulin PCR product (Fig. 2C) and scoring excision efficiency using PCR band intensity, the proportion of excised parasites was evaluated to be Ͼ90%, in agreement with previous uses of the UIS4/ FLP(Ϫ)F system (27,28,36,37).…”

Section: Table 1 Sub1/cond Sporozoites Are Unable To Establish a Bloosupporting

confidence: 80%

A Key Role for Plasmodium Subtilisin-like SUB1 Protease in Egress of Malaria Parasites from Host Hepatocytes

Tawk

Lacroix

Gueirard

et al. 2013

Journal of Biological Chemistry

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Background:The subtilisin-like SUB1 is involved in Plasmodium egress from erythrocytes. Results: Using conditional mutagenesis, we show that SUB1 plays an essential role during Plasmodium hepatic stages. Conclusion: SUB1 has a dual pivotal role in parasite egress from host hepatocytes and erythrocytes. Significance: Its critical involvement in hepatic and erythrocytic parasite development qualifies SUB1 as a multistage drug target.

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“…Although a TgAMA1-null mutant could be obtained in vitro 137 , the upregulation of TgAMA1 homologues that sustain residual invasion confirmed the crucial role of the moving junction in host cell penetration 134,138 . In Plasmodium spp., it was not possible to knockout AMA1 and RON4; however, the conditional depletion of P. berghei AMA1 (PbAMA1) and PfAMA1 caused a defect in merozoite invasion 139,140 and in the sealing of the parasitophorous vacuole at the end of invasion 140 . By contrast, the conditional depletion of PbAMA1 does not affect the entry of sporozoites 137,139 , but blocking the interaction of AMA1-RON2 with a 20-residue peptide -'R1 peptide' , which specifically binds AMA1 -inhibits hepatocyte invasion by P. falciparum sporozoites 141 .…”

Section: Box 2 | Transmembrane Adhesive Proteins Are Crucial For Glidmentioning

confidence: 99%

Gliding motility powers invasion and egress in Apicomplexa

et al. 2017

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| 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. NATURE REVIEWS | MICROBIOLOGYADVANCE ONLINE PUBLICATION | 1 REVIEWS © 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d . ToxoplasmosisA 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. SporozoitesThe infectious and motile stage produced in oocysts and transmitted by the definitive host. TachyzoitesThe motile and fast-replicative stage of Toxoplasma gondii that is able to invade any nucleated cell in the host. MerozoitesThe stage of Plasmodium spp. that infects erythrocytes, in which it initiates a new asexual life cycle. Actomyosin systemA complex that comprises actin filaments, myosin and associated proteins, and that is involved in movement. GlideosomeA molecular complex that powers gliding motility in apicomplexan parasites.motility, invasion and egress. In this Review, we focus primarily on the T. gondii tachyzoite, for which functional studies were first carried out, and we compare and contrast this with the motile stages of malaria parasites -the sporozoite, merozoite and ookinete.Emergence of the capping model The motility of Apicomplexa (historically named Sporozoa) has caught the attention of scientists for more than a century 8 and was named gliding motility early on, on the basis of microscopic observations Nature Reviews | Microbiology www.nature.com/nrmicro © 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d . of live specimens (FIG. 2; Supplementary information S1-S5 (movies)). This mode of motility differs substantially to amoeboid motion involving pseudopods, and from the ciliary and flagellar motion used by most unicellular organisms. The main hypothesis to explain gliding motility in the early days was slime secretion, as seen in slugs; ...

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Independent Roles of Apical Membrane Antigen 1 and Rhoptry Neck Proteins during Host Cell Invasion by Apicomplexa

Cited by 109 publications

References 42 publications

Expression and localization of rhoptry neck protein 5 in merozoites and sporozoites of Plasmodium yoelii

Expression and localization of rhoptry neck protein 5 in merozoites and sporozoites of Plasmodium yoelii

A Key Role for Plasmodium Subtilisin-like SUB1 Protease in Egress of Malaria Parasites from Host Hepatocytes

Gliding motility powers invasion and egress in Apicomplexa

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