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Malaria Journal
Published in: Malaria Journal 1/2011

Open Access 01-12-2011 | Research

Pv RON2, a new Plasmodium vivax rhoptry neck antigen

Authors: Gabriela Arévalo-Pinzón, Hernando Curtidor, Liliana C Patiño, Manuel A Patarroyo

Published in: Malaria Journal | Issue 1/2011

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Abstract

Background

Rhoptries are specialized organelles from parasites belonging to the phylum Apicomplexa; they secrete their protein content during invasion of host target cells and are sorted into discrete subcompartments within rhoptry neck or bulb. This distribution is associated with these proteins' role in tight junction (TJ) and parasitophorous vacuole (PV) formation, respectively.

Methods

Plasmodium falciparum RON2 amino acid sequence was used as bait for screening the codifying gene for the homologous protein in the Plasmodium vivax genome. Gene synteny, as well as identity and similarity values, were determined for ron2 and its flanking genes among P. falciparum, P. vivax and other malarial parasite genomes available at PlasmoDB and Sanger Institute databases. Pvron2 gene transcription was determined by RT-PCR of cDNA obtained from the P. vivax VCG-1 strain. Protein expression and localization were assessed by Western blot and immunofluorescence using polyclonal anti-Pv RON2 antibodies. Co-localization was confirmed using antibodies directed towards specific microneme and rhoptry neck proteins.

Results and discussion

The first P. vivax rhoptry neck protein (named here Pv RON2) has been identified in this study. Pv RON2 is a 2,204 residue-long protein encoded by a single 6,615 bp exon containing a hydrophobic signal sequence towards the amino-terminus, a transmembrane domain towards the carboxy-terminus and two coiled coil α-helical motifs; these are characteristic features of several previously described vaccine candidates against malaria. This protein also contains two tandem repeats within the interspecies variable sequence possibly involved in evading a host's immune system. Pv RON2 is expressed in late schizonts and localized in rhoptry necks similar to what has been reported for Pf RON2, which suggests its participation during target cell invasion.

Conclusions

The identification and partial characterization of the first P. vivax rhoptry neck protein are described in the present study. This protein is homologous to Pf RON2 which has previously been shown to be associated with Pf AMA-1, suggesting a similar role for Pv RON2.
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Literature
1.
Price RN, Tjitra E, Guerra CA, Yeung S, White NJ, Anstey NM: Vivax malaria: neglected and not benign. Am J Trop Med Hyg. 2007, 77: 79-87.PubMedCentralPubMed
2.
Greenwood BM, Fidock DA, Kyle DE, Kappe SH, Alonso PL, Collins FH, Duffy PE: Malaria: progress, perils, and prospects for eradication. J Clin Invest. 2008, 118: 1266-1276. 10.1172/JCI33996.PubMedCentralCrossRefPubMed
3.
Krotoski WA, Garnham PC, Cogswell FB, Collins WE, Bray RS, Gwasz RW, Killick-Kendrick R, Wolf RH, Sinden R, Hollingdale M, Lowrie RC, Koontz LC, Stanfill PS: Observations on early and late post-sporozoite tissue stages in primate malaria. IV. Pre-erythrocytic schizonts and/or hypnozoites of Chesson and North Korean strains of Plasmodium vivax in the chimpanzee. Am J Trop Med Hyg. 1986, 35: 263-274.PubMed
4.
5.
Bozdech Z, Mok S, Hu G, Imwong M, Jaidee A, Russell B, Ginsburg H, Nosten F, Day NP, White NJ, Carlton JM, Preiser PR: The transcriptome of Plasmodium vivax reveals divergence and diversity of transcriptional regulation in malaria parasites. Proc Natl Acad Sci USA. 2008, 105: 16290-16295. 10.1073/pnas.0807404105.PubMedCentralCrossRefPubMed
6.
Cowman AF, Crabb BS: Invasion of red blood cells by malaria parasites. Cell. 2006, 124: 755-766. 10.1016/j.cell.2006.02.006.CrossRefPubMed
7.
Blackman MJ, Bannister LH: Apical organelles of Apicomplexa: biology and isolation by subcellular fractionation. Mol Biochem Parasitol. 2001, 117: 11-25. 10.1016/S0166-6851(01)00328-0.CrossRefPubMed
8.
Preiser P, Kaviratne M, Khan S, Bannister L, Jarra W: The apical organelles of malaria merozoites: host cell selection, invasion, host immunity and immune evasion. Microbes Infect. 2000, 2: 1461-1477. 10.1016/S1286-4579(00)01301-0.CrossRefPubMed
9.
Carruthers VB, Sibley LD: Sequential protein secretion from three distinct organelles of Toxoplasma gondii accompanies invasion of human fibroblasts. Eur J Cell Biol. 1997, 73: 114-123.PubMed
10.
Aikawa M, Miller LH, Johnson J, Rabbege J: Erythrocyte entry by malarial parasites. A moving junction between erythrocyte and parasite. J Cell Biol. 1978, 77: 72-82. 10.1083/jcb.77.1.72.CrossRefPubMed
11.
Miller LH, Aikawa M, Johnson JG, Shiroishi T: Interaction between cytochalasin B-treated malarial parasites and erythrocytes. Attachment and junction formation. J Exp Med. 1979, 149: 172-184. 10.1084/jem.149.1.172.CrossRefPubMed
12.
Ward GE, Miller LH, Dvorak JA: The origin of parasitophorous vacuole membrane lipids in malaria-infected erythrocytes. J Cell Sci. 1993, 106 (Pt 1): 237-248.PubMed
13.
Baum J, Chen L, Healer J, Lopaticki S, Boyle M, Triglia T, Ehlgen F, Ralph SA, Beeson JG, Cowman AF: Reticulocyte-binding protein homologue 5 - an essential adhesin involved in invasion of human erythrocytes by Plasmodium falciparum. Int J Parasitol. 2009, 39: 371-380. 10.1016/j.ijpara.2008.10.006.CrossRefPubMed
14.
Duraisingh MT, Triglia T, Ralph SA, Rayner JC, Barnwell JW, McFadden GI, Cowman AF: Phenotypic variation of Plasmodium falciparum merozoite proteins directs receptor targeting for invasion of human erythrocytes. EMBO J. 2003, 22: 1047-1057. 10.1093/emboj/cdg096.PubMedCentralCrossRefPubMed
15.
Klotz FW, Hadley TJ, Aikawa M, Leech J, Howard RJ, Miller LH: A 60-kDa Plasmodium falciparum protein at the moving junction formed between merozoite and erythrocyte during invasion. Mol Biochem Parasitol. 1989, 36: 177-185. 10.1016/0166-6851(89)90190-4.CrossRefPubMed
16.
Hehl AB, Lekutis C, Grigg ME, Bradley PJ, Dubremetz JF, Ortega-Barria E, Boothroyd JC: Toxoplasma gondii homologue of plasmodium apical membrane antigen 1 is involved in invasion of host cells. Infect Immun. 2000, 68: 7078-7086. 10.1128/IAI.68.12.7078-7086.2000.PubMedCentralCrossRefPubMed
17.
Triglia T, Healer J, Caruana SR, Hodder AN, Anders RF, Crabb BS, Cowman AF: Apical membrane antigen 1 plays a central role in erythrocyte invasion by Plasmodium species. Mol Microbiol. 2000, 38: 706-718. 10.1046/j.1365-2958.2000.02175.x.CrossRefPubMed
18.
Besteiro S, Michelin A, Poncet J, Dubremetz JF, Lebrun M: Export of a Toxoplasma gondii rhoptry neck protein complex at the host cell membrane to form the moving junction during invasion. PLoS Pathog. 2009, 5: e1000309-10.1371/journal.ppat.1000309.PubMedCentralCrossRefPubMed
19.
Lamarque M, Besteiro S, Papoin J, Roques M, Vulliez-Le Normand B, Morlon-Guyot J, Dubremetz JF, Fauquenoy S, Tomavo S, Faber BW, Kocken CH, Thomas AW, Boulanger MJ, Bentley GA, Lebrun M: The RON2-AMA1 interaction is a critical step in moving junction-dependent invasion by Apicomplexan parasites. PLoS Pathog. 2011, 7: e1001276-10.1371/journal.ppat.1001276.PubMedCentralCrossRefPubMed
20.
Tyler JS, Boothroyd JC: The C-Terminus of Toxoplasma RON2 provides the crucial link between AMA1 and the host-associated invasion complex. PLoS Pathog. 2011, 7: e1001282-10.1371/journal.ppat.1001282.PubMedCentralCrossRefPubMed
21.
Cao J, Kaneko O, Thongkukiatkul A, Tachibana M, Otsuki H, Gao Q, Tsuboi T, Torii M: Rhoptry neck protein RON2 forms a complex with microneme protein AMA1 in Plasmodium falciparum merozoites. Parasitol Int. 2009, 58: 29-35. 10.1016/j.parint.2008.09.005.CrossRefPubMed
22.
Morahan BJ, Sallmann GB, Huestis R, Dubljevic V, Waller KL: Plasmodium falciparum: genetic and immunogenic characterisation of the rhoptry neck protein PfRON4. Exp Parasitol. 2009, 122: 280-288. 10.1016/j.exppara.2009.04.013.CrossRefPubMed
23.
Curtidor H, Patino LC, Arevalo-Pinzon G, Patarroyo ME, Patarroyo MA: Identification of the Plasmodium falciparum rhoptry neck protein 5 (PfRON5). Gene. 2011, 474: 22-28. 10.1016/j.gene.2010.12.005.CrossRefPubMed
24.
Alexander DL, Arastu-Kapur S, Dubremetz JF, Boothroyd JC: Plasmodium falciparum AMA1 binds a rhoptry neck protein homologous to TgRON4, a component of the moving junction in Toxoplasma gondii. Eukaryot Cell. 2006, 5: 1169-1173. 10.1128/EC.00040-06.PubMedCentralCrossRefPubMed
25.
Collins CR, Withers-Martinez C, Hackett F, Blackman MJ: An inhibitory antibody blocks interactions between components of the malarial invasion machinery. PLoS Pathog. 2009, 5: e1000273-10.1371/journal.ppat.1000273.PubMedCentralCrossRefPubMed
26.
Collins CR, Withers-Martinez C, Bentley GA, Batchelor AH, Thomas AW, Blackman MJ: Fine mapping of an epitope recognized by an invasion-inhibitory monoclonal antibody on the malaria vaccine candidate apical membrane antigen 1. J Biol Chem. 2007, 282: 7431-7441. 10.1074/jbc.M610562200.CrossRefPubMed
27.
Treeck M, Tamborrini M, Daubenberger CA, Gilberger TW, Voss TS: Caught in action: mechanistic insights into antibody-mediated inhibition of Plasmodium merozoite invasion. Trends Parasitol. 2009, 25: 494-497. 10.1016/j.pt.2009.07.008.CrossRefPubMed
28.
Harris KS, Casey JL, Coley AM, Masciantonio R, Sabo JK, Keizer DW, Lee EF, McMahon A, Norton RS, Anders RF, Foley M: Binding hot spot for invasion inhibitory molecules on Plasmodium falciparum apical membrane antigen 1. Infect Immun. 2005, 73: 6981-6989. 10.1128/IAI.73.10.6981-6989.2005.PubMedCentralCrossRefPubMed
29.
Richard D, MacRaild CA, Riglar DT, Chan JA, Foley M, Baum J, Ralph SA, Norton RS, Cowman AF: Interaction between Plasmodium falciparum apical membrane antigen 1 and the rhoptry neck protein complex defines a key step in the erythrocyte invasion process of malaria parasites. J Biol Chem. 2010, 285: 14815-14822. 10.1074/jbc.M109.080770.PubMedCentralCrossRefPubMed
30.
31.
32.
Combet C, Blanchet C, Geourjon C, Deleage G: NPS@: network protein sequence analysis. Trends Biochem Sci. 2000, 25: 147-150. 10.1016/S0968-0004(99)01540-6.CrossRefPubMed
33.
Nielsen H, Engelbrecht J, Brunak S, von Heijne G: Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites. Protein Eng. 1997, 10: 1-6. 10.1093/protein/10.1.1.CrossRefPubMed
34.
35.
Linding R, Russell RB, Neduva V, Gibson TJ: GlobPlot: Exploring protein sequences for globularity and disorder. Nucleic Acids Res. 2003, 31: 3701-3708. 10.1093/nar/gkg519.PubMedCentralCrossRefPubMed
36.
Letunic I, Goodstadt L, Dickens NJ, Doerks T, Schultz J, Mott R, Ciccarelli F, Copley RR, Ponting CP, Bork P: Recent improvements to the SMART domain-based sequence annotation resource. Nucleic Acids Res. 2002, 30: 242-244. 10.1093/nar/30.1.242.PubMedCentralCrossRefPubMed
37.
Newman AM, Cooper JB: XSTREAM: a practical algorithm for identification and architecture modeling of tandem repeats in protein sequences. BMC Bioinformatics. 2007, 8: 382-10.1186/1471-2105-8-382.PubMedCentralCrossRefPubMed
38.
39.
Geourjon C, Deleage G, Roux B: ANTHEPROT: an interactive graphics software for analyzing protein structures from sequences. J Mol Graph. 1991, 9: 188-190. 10.1016/0263-7855(91)80008-N. 167CrossRefPubMed
40.
Pico de Coana Y, Rodriguez J, Guerrero E, Barrero C, Rodriguez R, Mendoza M, Patarroyo MA: A highly infective Plasmodium vivax strain adapted to Aotus monkeys: quantitative haematological and molecular determinations useful for P. vivax malaria vaccine development. Vaccine. 2003, 21: 3930-3937. 10.1016/S0264-410X(03)00278-0.CrossRefPubMed
41.
Andrysiak PM, Collins WE, Campbell GH: Concentration of Plasmodium ovale- and Plasmodium vivax-infected erythrocytes from nonhuman primate blood using Percoll gradients. Am J Trop Med Hyg. 1986, 35: 251-254.PubMed
42.
Chomczynski P: A reagent for the single-step simultaneous isolation of RNA, DNA and proteins from cell and tissue samples. Biotechniques. 1993, 15: 532-534. 536-537PubMed
43.
Merrifield RB: Solid phase peptide synthesis. I. The synthesis of a tetrapeptide. Journal of American Chemical Society. 1963, 85: 2149-2154. 10.1021/ja00897a025.CrossRef
44.
Yandar N, Pastorin G, Prato M, Bianco A, Patarroyo ME, Manuel Lozano J: Immunological profile of a Plasmodium vivax AMA-1 N-terminus peptide-carbon nanotube conjugate in an infected Plasmodium berghei mouse model. Vaccine. 2008, 26: 5864-5873. 10.1016/j.vaccine.2008.08.014.CrossRefPubMed
45.
Mongui A, Perez-Leal O, Rojas-Caraballo J, Angel DI, Cortes J, Patarroyo MA: Identifying and characterising the Plasmodium falciparum RhopH3 Plasmodium vivax homologue. Biochem Biophys Res Commun. 2007, 358: 861-866. 10.1016/j.bbrc.2007.05.015.CrossRefPubMed
46.
Bozdech Z, Llinas M, Pulliam BL, Wong ED, Zhu J, DeRisi JL: The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum. PLoS Biol. 2003, 1: E5-10.1371/journal.pbio.0000005.PubMedCentralCrossRefPubMed
47.
Fidock DA, Gras-Masse H, Lepers JP, Brahimi K, Benmohamed L, Mellouk S, Guerin-Marchand C, Londono A, Raharimalala L, Meis JF, Langsley G, Roussilhon C, Tartar A, Druilhe P: Plasmodium falciparum liver stage antigen-1 is well conserved and contains potent B and T cell determinants. J Immunol. 1994, 153: 190-204.PubMed
48.
Gondeau C, Corradin G, Heitz F, Le Peuch C, Balbo A, Schuck P, Kajava AV: The C-terminal domain of Plasmodium falciparum merozoite surface protein 3 self-assembles into alpha-helical coiled coil tetramer. Mol Biochem Parasitol. 2009, 165: 153-161. 10.1016/j.molbiopara.2009.01.015.PubMedCentralCrossRefPubMed
49.
Villard V, Agak GW, Frank G, Jafarshad A, Servis C, Nebie I, Sirima SB, Felger I, Arevalo-Herrera M, Herrera S, Heitz F, Backer V, Druilhe P, Kajava AV, Corradin G: Rapid identification of malaria vaccine candidates based on alpha-helical coiled coil protein motif. PLoS One. 2007, 2: e645-10.1371/journal.pone.0000645.PubMedCentralCrossRefPubMed
50.
Kemp DJ, Coppel RL, Anders RF: Repetitive proteins and genes of malaria. Annu Rev Microbiol. 1987, 41: 181-208. 10.1146/annurev.mi.41.100187.001145.CrossRefPubMed
51.
Ramasamy R: Molecular basis for evasion of host immunity and pathogenesis in malaria. Biochim Biophys Acta. 1998, 1406: 10-27.CrossRefPubMed
52.
Alexander DL, Mital J, Ward GE, Bradley P, Boothroyd JC: Identification of the moving junction complex of Toxoplasma gondii: a collaboration between distinct secretory organelles. PLoS Pathog. 2005, 1: e17-10.1371/journal.ppat.0010017.PubMedCentralCrossRefPubMed
53.
Sadak A, Taghy Z, Fortier B, Dubremetz JF: Characterization of a family of rhoptry proteins of Toxoplasma gondii. Mol Biochem Parasitol. 1988, 29: 203-211. 10.1016/0166-6851(88)90075-8.CrossRefPubMed
54.
O'Donnell RA, Hackett F, Howell SA, Treeck M, Struck N, Krnajski Z, Withers-Martinez C, Gilberger TW, Blackman MJ: Intramembrane proteolysis mediates shedding of a key adhesin during erythrocyte invasion by the malaria parasite. J Cell Biol. 2006, 174: 1023-1033.PubMedCentralCrossRefPubMed
55.
Tufet-Bayona M, Janse CJ, Khan SM, Waters AP, Sinden RE, Franke-Fayard B: Localisation and timing of expression of putative Plasmodium berghei rhoptry proteins in merozoites and sporozoites. Mol Biochem Parasitol. 2009, 166: 22-31. 10.1016/j.molbiopara.2009.02.009.CrossRefPubMed
Metadata
Title
Pv RON2, a new Plasmodium vivax rhoptry neck antigen
Authors
Gabriela Arévalo-Pinzón
Hernando Curtidor
Liliana C Patiño
Manuel A Patarroyo
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2011
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-10-60

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