Unraveling the Elusive Rhoptry Exocytic Mechanism of Apicomplexa

Sparvoli, Daniela; Lebrun, Maryse

doi:10.1016/j.pt.2021.04.011

Cited by 24 publications

(23 citation statements)

References 112 publications

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“…5) compared to that of other apicomplexan parasites 17,20 . Recent comparative analyses between the apicomplexan rhoptry secretion system and the extrusome system in the related, free-living Ciliata phylum 36 suggests that the AV is an adaptation in Apicomplexa for parasitism, likely involved in the invasion of a host cell 10,17 . By resolving the apical vesicle in P. falciparum merozoites, we provide further evidence that this enigmatic vesicle is a conserved feature among apicomplexan parasites that may play a role in host cell invasion.…”

Section: Discussionmentioning

confidence: 99%

“…Upon recognition of a host red blood cell, a pair of club-shaped rhoptries in the Plasmodium merozoite secrete their contents into the cytosol of the host, permitting the merozoite's invasion and development within 7,9 . The mechanism by which rhoptries secrete their contents, and how proteins from inside the rhoptries are relocated across the rhoptry membrane, parasite plasma membrane, and host plasma membrane remain largely unknown 10 .…”

Section: Introductionmentioning

confidence: 99%

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In situ structure and priming mechanism of the rhoptry secretion system in Plasmodium revealed by cryo-electron tomography

Martinez

Chen

Cova

et al. 2022

Preprint

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Apicomplexan parasites secrete the contents of rhoptries into host cells to permit their invasion and establishment of an infectious niche. The rhoptry secretory apparatus (RSA), which is critical for rhoptry secretion, was recently discovered in Toxoplasma and Cryptosporidium. It is positioned at the cell apex and associates with an enigmatic apical vesicle (AV), which docks one or two rhoptries at the site of exocytosis. The interplay among the rhoptries, the AV, and the parasite plasma membrane for secretion remains unclear. Moreover, it is unknown if a similar machinery exists in the deadly malaria parasite Plasmodium falciparum. In this study, we use in situ cryo-electron tomography to investigate the rhoptry secretion system in P. falciparum merozoites. We identify the presence of an RSA at the cell apex and a morphologically distinct AV docking the tips of the two rhoptries to the RSA. We also discover two new organizations: one in which the AV is absent with one of the two rhoptry tips docks directly to the RSA, and a second in which the two rhoptries fuse together and the common tip docks directly to the RSA. Interestingly, rhoptries among the three states show no significant difference in luminal volume and density, suggesting that the exocytosis of rhoptry contents has not yet occurred, and that these different organizations likely represent sequential states leading to secretion. Using subtomogram averaging, we reveal different conformations of the RSA structure corresponding to each state, including the opening of a gate-like density in the rhoptry-fused state. These conformational changes of the RSA uncover structural details of a priming process for major rhoptry secretion, which likely occur after initial interaction with a red blood cell. Our results highlight a previously unknown step in the process of rhoptry secretion and indicate a regulatory role for the conserved apical vesicle in host invasion by apicomplexan parasites.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In situ structure and priming mechanism of the rhoptry secretion system in Plasmodium revealed by cryo-electron tomography

Martinez

Chen

Cova

et al. 2022

Preprint

Self Cite

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“…This was discussed again in 2021 by Sparvoli and collaborators in a recent review, discussing the limitations of studying rhoptry secretion due to the lack of inducers and the visualization an opening to the host cell (on several occasions) without a final confirmation whether the opening represents an open or transient pore. Nevertheless, rhoptry exportation through the pore has not been demonstrated so far [82]. Although the presence of ROPs in the host cytosol has not been directly observed in the Eimeria species, Diallo and collaborators [42] proved the interaction of EtROP1 with the host tumor protein p53, leading to the inhibition of host cell apoptosis and G0/G1 cell cycle arrest, supporting the idea of rhoptries reaching the host cytosol/nucleus.…”

Section: Regulation Of Protein Secretion From Micronemes and Rhoptriesmentioning

confidence: 98%

Do All Coccidia Follow the Same Trafficking Rules?

Marugán-Hernández

Sanchez-Arsuaga

Vaughan

et al. 2021

Life

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The Coccidia are a subclass of the Apicomplexa and include several genera of protozoan parasites that cause important diseases in humans and animals, with Toxoplasma gondii becoming the ‘model organism’ for research into the coccidian molecular and cellular processes. The amenability to the cultivation of T. gondii tachyzoites and the wide availability of molecular tools for this parasite have revealed many mechanisms related to their cellular trafficking and roles of parasite secretory organelles, which are critical in parasite-host interaction. Nevertheless, the extrapolation of the T. gondii mechanisms described in tachyzoites to other coccidian parasites should be done carefully. In this review, we considered published data from Eimeria parasites, a coccidian genus comprising thousands of species whose infections have important consequences in livestock and poultry. These studies suggest that the Coccidia possess both shared and diversified mechanisms of protein trafficking and secretion potentially linked to their lifecycles. Whereas trafficking and secretion appear to be well conversed prior to and during host-cell invasion, important differences emerge once endogenous development commences. Therefore, further studies to validate the mechanisms described in T. gondii tachyzoites should be performed across a broader range of coccidians (including T. gondii sporozoites). In addition, further genus-specific research regarding important disease-causing Coccidia is needed to unveil the individual molecular mechanisms of pathogenesis related to their specific lifecycles and hosts.

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“…It is an assembly of spirally arranged fibers originating from the preconoidal rings, at the distal tip of the structure, but also the polar ring, from which the 22 subpellicular microtubules originate, and two short intraconoidal microtubule [ 63 , 64 ]. This structure is closely associated with two different types of specialized apical secretory organelles called micronemes [ 65 ] and rhoptries [ 66 , 67 ], that secrete virulence factors that are essential for dissemination and survival of the parasites. Dense granules are another type of specialized secretory organelle that will later on release important factors for the intracellular establishment of the parasite [ 68 ], although these particular vesicles are not restricted to its apical part [ 69 ].…”

Section: Typical Ultrastructure Of a T Gondii Invasive Stagementioning

confidence: 99%

The pathogenicity and virulence of Toxoplasma gondii

Sanchez

Besteiro

2021

Virulence

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Toxoplasma gondii is a parasitic protist infecting a wide group of warm-blooded animals, ranging from birds to humans. While this infection is usually asymptomatic in healthy individuals, it can also lead to severe ocular or neurological outcomes in immunocompromised individuals or in developing fetuses. This obligate intracellular parasite has the ability to infect a considerable range of nucleated cells and can propagate in the intermediate host. Yet, under the pressure of the immune system it transforms into an encysted persistent form residing primarily in the brain and muscle tissues. Encysted parasites, which are resistant to current medication, may reactivate and give rise to an acute infection. The clinical outcome of toxoplasmosis depends on a complex balance between the host immune response and parasite virulence factors. Susceptibility to the disease is thus determined by both parasite strains and host species. Recent advances on our understanding of host cell-parasite interactions and parasite virulence have brought new insights into the pathophysiology of T. gondii infection and are summarized here.

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Unraveling the Elusive Rhoptry Exocytic Mechanism of Apicomplexa

Cited by 24 publications

References 112 publications

In situ structure and priming mechanism of the rhoptry secretion system in Plasmodium revealed by cryo-electron tomography

In situ structure and priming mechanism of the rhoptry secretion system in Plasmodium revealed by cryo-electron tomography

Do All Coccidia Follow the Same Trafficking Rules?

The pathogenicity and virulence of Toxoplasma gondii

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