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Published in: Malaria Journal 1/2013

Open Access 01-12-2013 | Research

A member of the CPW-WPC protein family is expressed in and localized to the surface of developing ookinetes

Authors: Niwat Kangwanrangsan, Mayumi Tachibana, Rachaneeporn Jenwithisuk, Takafumi Tsuboi, Suda Riengrojpitak, Motomi Torii, Tomoko Ishino

Published in: Malaria Journal | Issue 1/2013

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Abstract

Background

Despite the development of malaria control programs, billions of people are still at risk for this infectious disease. Recently, the idea of the transmission-blocking vaccine, which works by interrupting the infection of mosquitoes by parasites, has gained attention as a promising strategy for malaria control and eradication. To date, a limited number of surface proteins have been identified in mosquito-stage parasites and investigated as potential targets for transmission-blocking vaccines. Therefore, for the development of effective transmission-blocking strategies in epidemic areas, it is necessary to identify novel zygote/ookinete surface proteins as candidate antigens.

Methods

Since the expression of many zygote/ookinete proteins is regulated post-transcriptionally, proteins that are regulated by well-known translational mediators were focused. Through in silico screening, CPW-WPC family proteins were selected as potential zygote/ookinete surface proteins. All experiments were performed in the rodent malaria parasite, Plasmodium yoelii XNL. mRNA and protein expression profiles were examined by RT-PCR and western blotting, respectively, over the course of the life cycle of the malaria parasite. Protein function was also investigated by the generation of gene-disrupted transgenic parasites.

Results

The CPW-WPC protein family, named after the unique WxC repeat domains, is highly conserved among Plasmodium species. It is revealed that CPW-WPC mRNA transcripts are transcribed in gametocytes, while CPW-WPC proteins are expressed in zygote/ookinete-stage parasites. Localization analysis reveals that one of the CPW-WPC family members, designated as PyCPW-WPC-1, is a novel zygote/ookinete stage-specific surface protein. Targeted disruption of the pycpw-wpc-1 gene caused no obvious defects during ookinete and oocyst formation, suggesting that PyCPW-WPC-1 is not essential for mosquito-stage parasite development.

Conclusions

It is demonstrated that PyCPW-WPC-1 can be classified as a novel, post-transcriptionally regulated zygote/ookinete surface protein. Additional studies are required to determine whether all CPW-WPC family members are also present on the ookinete surface and share similar biological roles during mosquito-stage parasite development. Further investigations of CPW-WPC family proteins may facilitate understanding of parasite biology in the mosquito stage and development of transmission-blocking vaccines.
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Literature
1.
go back to reference World Health Organization: World Malaria Report. 2011, Geneva, Switzerland: World Health Organization World Health Organization: World Malaria Report. 2011, Geneva, Switzerland: World Health Organization
2.
go back to reference Murray CJL, Rosenfeld LC, Lim SS, Andrews KG, Foreman KJ, Haring D, Fullman N, Naghavi M, Lozano R, Lopez AD: Global malaria mortality between 1980 and 2010: a systemic analysis. Lancet. 2012, 379: 413-431. 10.1016/S0140-6736(12)60034-8.CrossRefPubMed Murray CJL, Rosenfeld LC, Lim SS, Andrews KG, Foreman KJ, Haring D, Fullman N, Naghavi M, Lozano R, Lopez AD: Global malaria mortality between 1980 and 2010: a systemic analysis. Lancet. 2012, 379: 413-431. 10.1016/S0140-6736(12)60034-8.CrossRefPubMed
3.
go back to reference Schwartz L, Brown GV, Genton B, Moorthy VS: A review of malaria vaccine clinical projects based on WHO rainbow table. Malar J. 2012, 11: 11-10.1186/1475-2875-11-11.PubMedCentralCrossRefPubMed Schwartz L, Brown GV, Genton B, Moorthy VS: A review of malaria vaccine clinical projects based on WHO rainbow table. Malar J. 2012, 11: 11-10.1186/1475-2875-11-11.PubMedCentralCrossRefPubMed
4.
go back to reference Breman JG, Brandling-Bennett AD: The challenge of malaria eradication in the twenty-first century: Research linked to operations is the key. Vaccine. 2011, 29S: D97-D103.CrossRef Breman JG, Brandling-Bennett AD: The challenge of malaria eradication in the twenty-first century: Research linked to operations is the key. Vaccine. 2011, 29S: D97-D103.CrossRef
5.
go back to reference Greenwood BM, Fidock DA, Kyle DE, Kappe SHI, Alonso PL, Collins FH, Duffy PE: Malaria: progress, perils, and prospects for eradication. J Clin Invest. 2008, 118: 1266-1276. 10.1172/JCI33996.PubMedCentralCrossRefPubMed Greenwood BM, Fidock DA, Kyle DE, Kappe SHI, Alonso PL, Collins FH, Duffy PE: Malaria: progress, perils, and prospects for eradication. J Clin Invest. 2008, 118: 1266-1276. 10.1172/JCI33996.PubMedCentralCrossRefPubMed
6.
go back to reference Genton B: Malaria vaccines: a toy for travellers or a tool for eradication?. Expert Rev Vaccine. 2008, 7: 597-611. 10.1586/14760584.7.5.597.CrossRef Genton B: Malaria vaccines: a toy for travellers or a tool for eradication?. Expert Rev Vaccine. 2008, 7: 597-611. 10.1586/14760584.7.5.597.CrossRef
7.
go back to reference Carter R: Transmission blocking malaria vaccines. Vaccine. 2001, 19: 2309-2314. 10.1016/S0264-410X(00)00521-1.CrossRefPubMed Carter R: Transmission blocking malaria vaccines. Vaccine. 2001, 19: 2309-2314. 10.1016/S0264-410X(00)00521-1.CrossRefPubMed
8.
go back to reference Ghosh A, Edwards MJ, Jacobs-Lorena : The journey of the malaria parasite in the mosquito: Hope for the new century. Parasitol Today. 2000, 16: 196-2001. 10.1016/S0169-4758(99)01626-9.CrossRefPubMed Ghosh A, Edwards MJ, Jacobs-Lorena : The journey of the malaria parasite in the mosquito: Hope for the new century. Parasitol Today. 2000, 16: 196-2001. 10.1016/S0169-4758(99)01626-9.CrossRefPubMed
9.
go back to reference Carter R, Kumar N, Quakyi I, Good M, Mendis K, Graves P, Miller L: Immunity to sexual stage of malaria parasites. Prog Allergy. 1988, 41: 193-214.PubMed Carter R, Kumar N, Quakyi I, Good M, Mendis K, Graves P, Miller L: Immunity to sexual stage of malaria parasites. Prog Allergy. 1988, 41: 193-214.PubMed
11.
go back to reference Scholz SM, Simon N, Lavazec C, Dude MA, Templeton TJ, Pradel G: Pf CCp proteins of Plasmodium falciparum: gametocyte-specific expression and role in complement-mediated inhibition of exflagellation. Int J Parasitol. 2008, 38: 327-340. 10.1016/j.ijpara.2007.08.009.CrossRefPubMed Scholz SM, Simon N, Lavazec C, Dude MA, Templeton TJ, Pradel G: Pf CCp proteins of Plasmodium falciparum: gametocyte-specific expression and role in complement-mediated inhibition of exflagellation. Int J Parasitol. 2008, 38: 327-340. 10.1016/j.ijpara.2007.08.009.CrossRefPubMed
12.
go back to reference Tsuboi T, Cao Y, Hitsumoto Y, Yanagi T, Kanbara H, Torii M: Two antigens on zygotes and ookinetes of Plasmodium yoelii and Plasmodium berghei that are distinct targets of transmission-blocking immunity. Infect Immun. 1997, 65: 2260-2264.PubMedCentralPubMed Tsuboi T, Cao Y, Hitsumoto Y, Yanagi T, Kanbara H, Torii M: Two antigens on zygotes and ookinetes of Plasmodium yoelii and Plasmodium berghei that are distinct targets of transmission-blocking immunity. Infect Immun. 1997, 65: 2260-2264.PubMedCentralPubMed
13.
go back to reference Billker O, Dechamps S, Tewari R, Wenig G, Franke-Fayard B, Brinkmann V: Calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in malaria parasite. Cell. 2004, 117: 503-514. 10.1016/S0092-8674(04)00449-0.CrossRefPubMed Billker O, Dechamps S, Tewari R, Wenig G, Franke-Fayard B, Brinkmann V: Calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in malaria parasite. Cell. 2004, 117: 503-514. 10.1016/S0092-8674(04)00449-0.CrossRefPubMed
14.
go back to reference van Dijk MR, Janse CJ, Thompson J, Waters AP, Braks JA, Dodemont HJ, Stunnenberg HG, van Gemert G, Sauerwein RW, Eling W: A central role for P48/45 in malaria parasite male gamete fertility. Cell. 2001, 104: 153-164. 10.1016/S0092-8674(01)00199-4.CrossRefPubMed van Dijk MR, Janse CJ, Thompson J, Waters AP, Braks JA, Dodemont HJ, Stunnenberg HG, van Gemert G, Sauerwein RW, Eling W: A central role for P48/45 in malaria parasite male gamete fertility. Cell. 2001, 104: 153-164. 10.1016/S0092-8674(01)00199-4.CrossRefPubMed
15.
go back to reference Liu Y, Tewari R, Ning J, Blagborough AM, Garbom S, Pei J, Grishin NV, Steele RE, Sinden RE, Snell WJ, Billker O: The conserved plant sterility gene HAP2 functions after attachment of fusogenic membranes in Chlamydomonas and Plasmodium gametes. Genes Dev. 2008, 22: 1051-1068. 10.1101/gad.1656508.PubMedCentralCrossRefPubMed Liu Y, Tewari R, Ning J, Blagborough AM, Garbom S, Pei J, Grishin NV, Steele RE, Sinden RE, Snell WJ, Billker O: The conserved plant sterility gene HAP2 functions after attachment of fusogenic membranes in Chlamydomonas and Plasmodium gametes. Genes Dev. 2008, 22: 1051-1068. 10.1101/gad.1656508.PubMedCentralCrossRefPubMed
16.
go back to reference Hirai M, Arai M, Mori T, Miyagishima S, Kawai S, Kita K, Kuroiwa T, Terenius O, Matsuoka H: Male fertility of malaria parasites is determined by GCS1, a plant-type reproduction factor. Curr Biol. 2008, 18: 607-613. 10.1016/j.cub.2008.03.045.CrossRefPubMed Hirai M, Arai M, Mori T, Miyagishima S, Kawai S, Kita K, Kuroiwa T, Terenius O, Matsuoka H: Male fertility of malaria parasites is determined by GCS1, a plant-type reproduction factor. Curr Biol. 2008, 18: 607-613. 10.1016/j.cub.2008.03.045.CrossRefPubMed
17.
go back to reference Angrisano F, Tan Y, Sturm A, Baum J: Malaria parasite colonisation of the mosquito midgut – Placing the Plasmodium ookinete centre stage. Int J Parasitol. 2012, 42: 519-527. 10.1016/j.ijpara.2012.02.004.CrossRefPubMed Angrisano F, Tan Y, Sturm A, Baum J: Malaria parasite colonisation of the mosquito midgut – Placing the Plasmodium ookinete centre stage. Int J Parasitol. 2012, 42: 519-527. 10.1016/j.ijpara.2012.02.004.CrossRefPubMed
18.
go back to reference Mair GR, Braks JAM, Garver LS, Wiegant JCAG, Hall N, Dirks RW, Khan SM, Dimopoulos G, Janse CJ, Waters AP: Regulation of sexual development of Plasmodium by translational repression. Science. 2006, 313: 667-669. 10.1126/science.1125129.PubMedCentralCrossRefPubMed Mair GR, Braks JAM, Garver LS, Wiegant JCAG, Hall N, Dirks RW, Khan SM, Dimopoulos G, Janse CJ, Waters AP: Regulation of sexual development of Plasmodium by translational repression. Science. 2006, 313: 667-669. 10.1126/science.1125129.PubMedCentralCrossRefPubMed
19.
go back to reference Mair GR, Lasonder E, Garver LS, Franke-Fayard BMD, Carret CK, Wiegant JCAG, Dirks RW, Dimopoulos G, Janse CJ, Waters AP: Universal features of post-transcriptional gene regulation are critical for Plasmodium zygote development. PLoS Pathog. 2010, 6: 1-12.CrossRef Mair GR, Lasonder E, Garver LS, Franke-Fayard BMD, Carret CK, Wiegant JCAG, Dirks RW, Dimopoulos G, Janse CJ, Waters AP: Universal features of post-transcriptional gene regulation are critical for Plasmodium zygote development. PLoS Pathog. 2010, 6: 1-12.CrossRef
21.
go back to reference Tsuboi T, Takeo S, Iriko H, Jin L, Tsuchimochi M, Matsuda S, Han E, Otsuki H, Kaneko O, Sattabongkot J, Udomsangpetch R, Sawasaki T, Torii M, Endo Y: Wheat germ cell-free system-based production of malaria proteins for discovery of novel vaccine candidates. Infect Immun. 2008, 76: 1702-1708. 10.1128/IAI.01539-07.PubMedCentralCrossRefPubMed Tsuboi T, Takeo S, Iriko H, Jin L, Tsuchimochi M, Matsuda S, Han E, Otsuki H, Kaneko O, Sattabongkot J, Udomsangpetch R, Sawasaki T, Torii M, Endo Y: Wheat germ cell-free system-based production of malaria proteins for discovery of novel vaccine candidates. Infect Immun. 2008, 76: 1702-1708. 10.1128/IAI.01539-07.PubMedCentralCrossRefPubMed
22.
go back to reference Sawasaki T, Ogasawara T, Morishita R, Endo Y: A cell-free protein synthesis system for high-throughput proteomics. Proc Natl Acad Sci USA. 2002, 99: 14652-14657. 10.1073/pnas.232580399.PubMedCentralCrossRefPubMed Sawasaki T, Ogasawara T, Morishita R, Endo Y: A cell-free protein synthesis system for high-throughput proteomics. Proc Natl Acad Sci USA. 2002, 99: 14652-14657. 10.1073/pnas.232580399.PubMedCentralCrossRefPubMed
23.
go back to reference Takai K, Sawasaki T, Endo Y: Practical cell-free protein synthesis system using purified wheat embryos. Nat Protoc. 2010, 5: 227-238. 10.1038/nprot.2009.207.CrossRefPubMed Takai K, Sawasaki T, Endo Y: Practical cell-free protein synthesis system using purified wheat embryos. Nat Protoc. 2010, 5: 227-238. 10.1038/nprot.2009.207.CrossRefPubMed
24.
go back to reference Otsuki H, Kaneko O, Thongkukiatkul A, Tachibana M, Iriko H, Takeo S, Tsuboi T, Torii M: Single amino acid substitution in Plasmodium yoelii erythrocyte ligand determines its localization and controls parasite virulence. Proc Natl Acad Sci USA. 2009, 106: 7167-7172. 10.1073/pnas.0811313106.PubMedCentralCrossRefPubMed Otsuki H, Kaneko O, Thongkukiatkul A, Tachibana M, Iriko H, Takeo S, Tsuboi T, Torii M: Single amino acid substitution in Plasmodium yoelii erythrocyte ligand determines its localization and controls parasite virulence. Proc Natl Acad Sci USA. 2009, 106: 7167-7172. 10.1073/pnas.0811313106.PubMedCentralCrossRefPubMed
25.
go back to reference Aurrecoechea C, Brestelli J, Brunk BP, Carlton JM, Dommer J, Fischer S, Gajria B, Gao X, Gingle A, Grant G, Harb OS, Heiges M, Innamorato F, Iodice J, Kissinger JC, Kraemer E, Li W, Miller JA, Morrison HG, Nayak V, Pennington C, Pinney DF, Roos DS, Ross C, Stoeckert CJ, Sullivan S, Treatman C, Wang H: PlasmoDB: a functional genomic database for malaria parasites. Nucleic Acids Res. 2009, 37: D539-D543. 10.1093/nar/gkn814.PubMedCentralCrossRefPubMed Aurrecoechea C, Brestelli J, Brunk BP, Carlton JM, Dommer J, Fischer S, Gajria B, Gao X, Gingle A, Grant G, Harb OS, Heiges M, Innamorato F, Iodice J, Kissinger JC, Kraemer E, Li W, Miller JA, Morrison HG, Nayak V, Pennington C, Pinney DF, Roos DS, Ross C, Stoeckert CJ, Sullivan S, Treatman C, Wang H: PlasmoDB: a functional genomic database for malaria parasites. Nucleic Acids Res. 2009, 37: D539-D543. 10.1093/nar/gkn814.PubMedCentralCrossRefPubMed
26.
go back to reference Gissot M, Ting L, Daly TM, Bergman LW, Sinnis P, Kim K: High mobility group protein HMGB2 is a critical regulator of Plasmodium oocyst development. J Biol Chem. 2008, 283: 17030-17038. 10.1074/jbc.M801637200.PubMedCentralCrossRefPubMed Gissot M, Ting L, Daly TM, Bergman LW, Sinnis P, Kim K: High mobility group protein HMGB2 is a critical regulator of Plasmodium oocyst development. J Biol Chem. 2008, 283: 17030-17038. 10.1074/jbc.M801637200.PubMedCentralCrossRefPubMed
27.
go back to reference Bushell ESC, Ecker A, Schlegelmilch T, Goulding D, Dougan G, Sinden RE, Christophides GK, Kafatos FC, Vlachou D: Paternal effect of the nuclear formin-like protein MISFIT on Plasmodium development in the mosquito vector. PLoS Pathog. 2009, 5: e1000539-10.1371/journal.ppat.1000539.PubMedCentralCrossRefPubMed Bushell ESC, Ecker A, Schlegelmilch T, Goulding D, Dougan G, Sinden RE, Christophides GK, Kafatos FC, Vlachou D: Paternal effect of the nuclear formin-like protein MISFIT on Plasmodium development in the mosquito vector. PLoS Pathog. 2009, 5: e1000539-10.1371/journal.ppat.1000539.PubMedCentralCrossRefPubMed
28.
go back to reference Ansari FA, Kumar N, Subramanyam MB, Gnanamani M, Ramachandran S: MAAP: Malaria adhesins and adhesin-like proteins predictor. Proteins. 2008, 70: 659-666.CrossRefPubMed Ansari FA, Kumar N, Subramanyam MB, Gnanamani M, Ramachandran S: MAAP: Malaria adhesins and adhesin-like proteins predictor. Proteins. 2008, 70: 659-666.CrossRefPubMed
30.
go back to reference Tomas AM, Margos G, Dimopoulos G, van Lin LH, Koning-Ward TF, Sinha R, Lupetti P, Beetsma AL, Rodriguez MC, Karras M, Hager A, Mendoza J, Butcher GA, Kafatos F, Janse CJ, Waters AP, Sinden RE: P25 and P28 proteins of the malaria ookinete surface have multiple and partially redundant functions. EMBO J. 2001, 20: 3975-3983. 10.1093/emboj/20.15.3975.PubMedCentralCrossRefPubMed Tomas AM, Margos G, Dimopoulos G, van Lin LH, Koning-Ward TF, Sinha R, Lupetti P, Beetsma AL, Rodriguez MC, Karras M, Hager A, Mendoza J, Butcher GA, Kafatos F, Janse CJ, Waters AP, Sinden RE: P25 and P28 proteins of the malaria ookinete surface have multiple and partially redundant functions. EMBO J. 2001, 20: 3975-3983. 10.1093/emboj/20.15.3975.PubMedCentralCrossRefPubMed
Metadata
Title
A member of the CPW-WPC protein family is expressed in and localized to the surface of developing ookinetes
Authors
Niwat Kangwanrangsan
Mayumi Tachibana
Rachaneeporn Jenwithisuk
Takafumi Tsuboi
Suda Riengrojpitak
Motomi Torii
Tomoko Ishino
Publication date
01-12-2013
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2013
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-12-129

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