Rhoptry neck protein RON2 forms a complex with microneme protein AMA1 in Plasmodium falciparum merozoites

Cao, Jun; Kaneko, O.; Thongkukiatkul, Amporn; Tachibana, Masashi; Otsuki, Hitoshi; Gao, Qi; Tsuboi, Takafumi; Torii, Motomi

doi:10.1016/j.parint.2008.09.005

Cited by 156 publications

(146 citation statements)

References 32 publications

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“…3) was not detected even in the precipitate with anti-PyRON5, suggesting that the epitope region in the ~87-kDa PyRON5 product is not recognized by immunoprecipitation with this anti-PyRON5 antibody. In the precipitates with antiPyRON2, anti-PyRON4, and anti-PyAMA1, all of these proteins were detected, except PyRON2 in the precipitate with anti-PyAMA1, which is consistent with previous reports that failed or had difficulty to detect PfRON2 in precipitate with anti-PfAMA1 [3,4]. The band detected at ~100 kDa by anti-PyRON5 antibody was seen only in precipitates with rabbit control and anti-PyRON5, not in the Tx extract input, indicating that this is unrelated to RON5.…”

Section: Complex Formation Of Pyron5 With Pyron4 Pyron2 and Pyama1supporting

confidence: 91%

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: Complex Formation Of Pyron5 With Pyron4 Pyron2 and Pyama1supporting

confidence: 91%

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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“…Another antigen in our Top 20 list, Rhoptry neck protein 3 (RON3, PFL2505c), is expressed in sporozoites (17) and this family of proteins is reported to be important for parasite invasion and the formation of the parasitophorous vacuole (84 -86). A complex of RON2, RON4, and AMA1 localizes to the moving junction formed at invasion (87,88). AMA1 is a critical sporozoite protein for hepatocyte invasion (89) and is also in our Top 20 list.…”

Section: Discussionmentioning

confidence: 99%

Sterile Protective Immunity to Malaria is Associated with a Panel of Novel P. falciparum Antigens

Trieu

Kayala

Burk

et al. 2011

Molecular & Cellular Proteomics

140

155

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The development of an effective malaria vaccine remains a global public health priority. Less than 0.5% of the Plasmodium falciparum genome has been assessed as potential vaccine targets and candidate vaccines have been based almost exclusively on single antigens. It is possible that the failure to develop a malaria vaccine despite decades of effort might be attributed to this historic focus. To advance malaria vaccine development, we have fabricated protein microarrays representing 23% of the entire P. falciparum proteome and have probed these arrays with plasma from subjects with sterile protection or no protection after experimental immunization with radiation attenuated P. falciparum sporozoites. A panel of 19 pre-erythrocytic stage antigens was identified as strongly associated with sporozoite-induced protective immunity; 16 of these antigens were novel and 85% have been independently identified in sporozoite and/or liver stage proteomic or transcriptomic data sets. Reactivity to any individual antigen did not correlate with protection but there was a highly significant difference in the cumulative signal intensity between protected and not protected individuals. Functional annotation indicates that most of these signature proteins are involved in cell cycle/DNA processing and protein synthesis. In addition, 21 novel blood-stage specific antigens were identified. Our data provide the first evidence that sterile protective immunity against malaria is directed against a panel of novel P. falciparum antigens rather than one antigen in isolation. These results have important implications for vaccine development, suggesting that an efficacious malaria vaccine should be multivalent and targeted at a select panel of key antigens, many of which have not been previously

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“…Like other Apicomplexan parasites, Plasmodium species engage a group of proteins referred to as Rhoptries Neck (RON proteins) to interact with micronemal protein Apial Membrane Antigen-1 (AMA-1). This interaction results in a formation of a complex called Moving Junction (MJ) [51][52][53][54][55]. In Plasmodium falciparum, three RONs namely PfRON2, PfRON4 and PfRON5 are found to interact with the Plasmodium falciparum AMA-1 (PfAMA-1) to form Moving Junction.…”

Section: Apical Merozoite Antigens (Amas) and Ron Proteinsmentioning

confidence: 99%

Preliminary Investigations into the Binding Interactions between Plasmodial and Host Proteins using Computational Approaches

Nwankwo¹

2012

JPB

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Rhoptry neck protein RON2 forms a complex with microneme protein AMA1 in Plasmodium falciparum merozoites

Cited by 156 publications

References 32 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

Sterile Protective Immunity to Malaria is Associated with a Panel of Novel P. falciparum Antigens

Preliminary Investigations into the Binding Interactions between Plasmodial and Host Proteins using Computational Approaches

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