Plasmodium rhoptries: how things went pear-shaped

Kats, Lev; Black, Casilda Gabrielle; Proellocks, Nicholas Ian; Coppel, Ross L.

doi:10.1016/j.pt.2006.04.001

Cited by 62 publications

(84 citation statements)

References 89 publications

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“…Some rhoptry neck proteins (RONs) are conserved between Toxoplasma, Eimeria, and Plasmodium [6][7][8], whereas rhoptry bulb proteins (ROPs) are generally distinct in each species (reviewed in [7]), presumably a consequence of the different host cells (nucleated vs non-nucleated) that each species invades. To date, more than 30 proteins have been classified as rhoptry proteins in the human malaria parasite Plasmodium falciparum (Figure 1) [9][10][11]. A further 27 potential rhoptry proteins with unknown functions have been identified through proteome analysis of purified rhoptries from the rodent species Plasmodium yoelii [12].…”

Section: The Rhoptries and Its Constituentsmentioning

confidence: 99%

“…The same is likely to be the case for RAP3 given that RAP2 and RAP3 are paralogs. The high molecular weight RhopH complex (reviewed in [9]) is formed via non-covalent interactions; whether their association is required to ensure correct localization to the rhoptries remains to be investigated.…”

Section: The Rhoptries and Its Constituentsmentioning

confidence: 99%

“…RAP1 is also immunogenic because anti-RAP1 can be detected in the sera of naturally infected hosts, although vaccines directed against this protein do not protect completely against challenge infection (reviewed in [9]). This lack of protection is consistent with what we now know about the sequence of invasion, which has revealed that ROPs are actually secreted into the PV/PVM after formation of the TJ [53].…”

Section: Rhoptry Bulb Proteins Function Predominantly Downstream Of Imentioning

confidence: 99%

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Plasmodium rhoptry proteins: why order is important

Counihan

Kalanon

Coppel

et al. 2013

Trends in Parasitology

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101

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Section: The Rhoptries and Its Constituentsmentioning

confidence: 99%

Section: The Rhoptries and Its Constituentsmentioning

confidence: 99%

Section: Rhoptry Bulb Proteins Function Predominantly Downstream Of Imentioning

confidence: 99%

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Plasmodium rhoptry proteins: why order is important

Counihan

Kalanon

Coppel

et al. 2013

Trends in Parasitology

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101

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“…These organelles include the rhoptries, micronemes, and dense granules (54,56,57). The contents of these organelles are essential for parasite invasion into host cells and their intracellular replication, survival, and further transmission.…”

Section: Glp_158_56914_57444 (29250378)mentioning

confidence: 99%

Centrins, Cell Cycle Regulation Proteins in Human Malaria Parasite Plasmodium falciparum

Mahajan

Selvapandiyan

Gerald

et al. 2008

Journal of Biological Chemistry

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Molecules and cellular mechanisms that regulate the process of cell division in malaria parasites remain poorly understood. In this study we isolate and characterize the four Plasmodium falciparum centrins (PfCENs) and, by growth complementation studies, provide evidence for their involvement in cell division. Centrins are cytoskeleton proteins with key roles in cell division, including centrosome duplication, and possess four Ca 2؉ -binding EF hand domains. By means of phylogenetic analysis, we were able to decipher the evolutionary history of centrins in eukaryotes with particular emphasis on the situation in apicomplexans and other alveolates. Plasmodium possesses orthologs of four distinct centrin paralogs traceable to the ancestral alveolate, including two that are unique to alveolates. By real time PCR and/or immunofluorescence, we determined the expression of PfCEN mRNA or protein in sporozoites, asexual blood forms, gametocytes, and in the oocysts developing inside mosquito mid-gut. Immunoelectron microscopy studies showed that centrin is expressed in close proximity with the nucleus of sporozoites and asexual schizonts. Furthermore, confocal and widefield microscopy using the double staining with ␣-tubulin and centrin antibodies strongly suggested that centrin is associated with the parasite centrosome. Following the episomal expression of the four PfCENs in a centrin knock-out Leishmania donovani parasite line that exhibited a severe growth defect, one of the PfCENs was able to partially restore Leishmania growth rate and overcome the defect in cytokinesis in such mutant cell line. To our knowledge, this study is the first characterization of a Plasmodium molecule that is involved in the process of cell division. These results provide the opportunity to further explore the role of centrins in cell division in malaria parasites and suggest novel targets to construct genetically modified, live attenuated malaria vaccines.

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“…In addition, merozoites are briefly exposed to the host immune system during RBC egress and invasion. As such, proteins on the surface of merozoites or those that are secreted during invasion are potential targets for neutralising antibodies and potential candidates for vaccine development (Cowman et al, 2002;Cowman and Crabb, 2006;Kats et al, 2006). GPIanchored proteins have emerged as important candidates for inclusion in a blood-stage subunit vaccine.…”

Section: Introductionmentioning

confidence: 99%

Plasmodium falciparum Pf34, a novel GPI-anchored rhoptry protein found in detergent-resistant microdomains

Proellocks

Kovacevic

Ferguson

et al. 2007

International Journal for Parasitology

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Apicomplexan parasites are characterised by the presence of specialised organelles, such as rhoptries, located at the apical end of invasive forms that play an important role in invasion of the host cell and formation of the parasitophorous vacuole. In this study, we have characterised a novel Plasmodium falciparum rhoptry protein, Pf34, encoded by a single exon gene located on chromosome 4 and expressed as a 34 kDa protein in mature asexual stage parasites. Pf34 is expressed later in the life cycle than the previously described rhoptry protein, Rhoptry Associated Membrane Antigen (RAMA). Orthologues of Pf34 are present in other Plasmodium species and a potential orthologue has also been identified in Toxoplasma gondii. Indirect immunofluorescence assays show that Pf34 is located at the merozoite apex and localises to the rhoptry neck. Pf34, previously demonstrated to be glutathione-S-transferase (GPI)-anchored (Gilson et al., 2006, Identification and stoichiometry of GPI-anchored membrane proteins of the human malaria parasite Plasmodium falciparum. Mol Cell Proteomics, 1286-1299), is associated with parasite-derived detergent-resistant microdomains (DRMs). Pf34 is carried into the newly invaded ring, consistent with a role for Pf34 in the formation of the parasitophorous vacuole. Pf34 is exposed to the human immune system during infection and is recognised by human immune sera collected from residents of malaria endemic areas of Vietnam and Papua New Guinea.

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Plasmodium rhoptries: how things went pear-shaped

Cited by 62 publications

References 89 publications

Plasmodium rhoptry proteins: why order is important

Plasmodium rhoptry proteins: why order is important

Centrins, Cell Cycle Regulation Proteins in Human Malaria Parasite Plasmodium falciparum

Plasmodium falciparum Pf34, a novel GPI-anchored rhoptry protein found in detergent-resistant microdomains

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