Skip to main content Accessibility help

Proteins of the malaria parasite sexual stages: expression, function and potential for transmission blocking strategies

  • G. PRADEL (a1)


The sexual phase of the malaria pathogen, Plasmodium falciparum, culminates in fertilization within the midgut of the mosquito and represents a crucial step in the completion of the parasite's life-cycle and transmission of the disease. Two decades ago, the first sexual stage-specific surface proteins were identified, among them Pfs230, Pfs48/45, and Pfs25, which were of scientific interest as candidates for the development of transmission blocking vaccines. A decade later, gene information gained from the sequencing of the P. falciparum genome led to the identification of numerous additional sexual-stage proteins with antigenic properties and novel enzymes that putatively possess regulatory functions during sexual-stage development. This review aims to summarize the sexual-stage proteins identified to date, to compare their stage specificities and expression patterns and to highlight novel regulative mechanisms of sexual differentiation. The prospective candidacy of select sexual-stage proteins as targets for transmission blocking strategies will be discussed.


Corresponding author

*Corresponding author. Tel: +49 931 312174. Fax: +49 931 312578. E-mail:


Hide All
Alano, P. and Billker, O. (2005). Gametocytes and gametes. In Molecular Approaches to Malaria (ed. Sherman, I. W.), pp. 191219. ASM Press, Washington.
Alano, P., Premawansa, S., Bruce, M. C. and Carter, R. (1991). A stage specific gene expressed at the onset of gametocytogenesis in Plasmodium falciparum. Molecular and Biochemical Parasitology 46, 8188.
Alano, P., Read, D., Bruce, M., Aikawa, M., Kaido, T., Tegoshi, T., Bhatti, S., Smith, D. K., Luo, C., Hansra, S., Carter, R. and Elliott, J. F. (1995). COS cell expression cloning of Pfg377, a Plasmodium falciparum gametocyte antigen associated with osmiophilic bodies. Molecular and Biochemical Parasitology 74, 143156.
Anamika, Srinivasan, N. and Krupa, A. (2005). A genomic perspective of protein kinases in Plasmodium falciparum. Proteins 58, 180189.
Arakawa, T., Komesu, A., Otsuki, H., Sattabongkot, J., Udomsangpetch, R., Matsumoto, Y., Tsuji, N., Wu, Y., Torii, M. and Tsuboi, T. (2005). Nasal immunization with a malaria transmission-blocking vaccine candidate, P25, induces complete protective immunity in mice against field isolates of Plasmodium falciparum. Infection and Immunity 73, 73757380.
Baker, D. A., Daramola, O., McCrossan, M. V., Harmer, J. and Targett, G. A.& T. (1994). Subcellular localization of Pfs16, a Plasmodium falciparum gametocyte antigen. Parasitology 108, 129137.
Barnes, D. A., Thompson, J., Triglia, T., Day, K. and Kemp, D. J. (1994). Mapping the genetic locus implicated in cytoadherence of Plasmodium falciparum to melanoma cells. Molecular and Biochemical Parasitology 66, 2129.
Billker, O., Dechamps, S., Tewari, R., Wenig, G., Franke-Fayard, B. and Brinkmann, V. (2004). Calcium and a calcium-dependent protein kinase regulate gamete formation and mosquito transmission in a malaria parasite. Cell 117, 503514.
Billker, O., Lindo, V., Panico, M., Etienne, A. E., Paxton, T., Dell, A., Rogers, M., Sinden, R. E. and Morris, H. R. (1998). Identification of xanthurenic acid as the putative inducer of malaria development in the mosquito. Nature, London 392, 289292.
Billker, O., Shaw, M. K., Margos, G. and Sinden, R. E. (1997). The roles of temperature, pH and mosquito factors as triggers of male and female gametogenesis of Plasmodium berghei in vitro. Parasitology. 115, 17.
Brooks, S. R. and Williamson, K. C. (2000). Proteolysis of Plasmodium falciparum surface antigen, Pfs230, during gametogenesis. Molecular and Biochemical Parasitology 106, 7782.
Bruce, M. C., Carter, R. N., Nakamura, K., Aikawa, M. and Carter, R. (1994). Cellular location and temporal expression of Plasmodium falciparum sexual stage antigen Pfs16. Molecular and Biochemical Parasitology 65, 1122.
Bustamante, P. J., Woodruff, D. C., Oh, J., Keister, D. B., Muratova, O. and Williamson, K. C. (2000). Differential ability of specific regions of Plasmodium falciparum sexual-stage antigen, Pfs230, to induce malaria transmission-blocking immunity. Parasite Immunology 22, 373380.
Carlton, J. M., Angiuoli, S. V., Suh, B. B., Kooij, T. W., Pertea, M., Silva, J. C., Ermolaeva, M. D., Allen, J. E., Selengut, J. D., Koo, H. L., Peterson, J. D., Pop, M., Kosack, D. S., Shumway, M. F., Bidwell, S. L., Shallom, S. J., van Aken, S. E., Riedmuller, S. B., Feldblyum, T. V., Cho, J. K., Quackenbush, J., Sedegah, M., Shoaibi, A., Cummings, L. M., Florens, L., Yates, J. R., Raine, J. D., Sinden, R. E., Harris, M. A., Cunningham, D. A., Preiser, P. R., Bergman, L. W., Vaidya, A. B., van Lin, L. H., Janse, C. J., Waters, A. P., Smith, H. O., White, O. R., Salzberg, S. L., Venter, J. C., Fraser, C. M., Hoffman, S. L., Gardner, M. J. and Carucci, D. J. (2002). Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii. Nature, London 419, 512519.
Carter, R. (2001). Transmission blocking malaria vaccines. Vaccine 19, 23092314.
Carter, R. and Chen, D. H. (1976). Malaria transmission blocked by immunisation with gametes of the malaria parasite. Nature, London 263, 5760.
Carter, R., Coulson, A., Bhatti, S., Taylor, B. J. and Elliott, J. F. (1995). Predicted disulfide-bonded structures for three uniquely related proteins of Plasmodium falciparum, Pfs230, Pfs48/45 and Pf12. Molecular and Biochemical Parasitology 71, 203210.
Carter, R., Graves, P. M., Creasey, A., Byrne, K., Read, D., Alano, P. and Fenton, B. (1989). Plasmodium falciparum: an abundant stage-specific protein expressed during early gametocyte development. Experimental Parasitology 69, 140149.
Carter, R., Mendis, K. N., Miller, L. H., Molineaux, L. and Saul, A. (2000). Malaria transmission-blocking vaccines–how can their development be supported? Nature Medicine 6, 241244.
Carucci, D. J., Witney, A. A., Muhia, D. K., Warhurst, D. C., Schaap, P., Meima, M., Li, J. L., Taylor, M. C., Kelly, J. M. and Baker, D. A. (2000). Guanylyl cyclase activity associated with putative bifunctional integral membrane proteins in Plasmodium falciparum. Journal of Biological Chemistry 275, 2214722156.
Catteruccia, F. (2007). Malaria vector control in the third millennium: progress and perspectives of molecular approaches. Pest Management Science 63, 634640.
Claudianos, C., Dessens, J. T., Trueman, H. E., Arai, M., Mendoza, J., Butcher, G. A., Crompton, T. and Sinden, R. E. (2002). A malaria scavenger receptor-like protein essential for parasite development. Molecular Microbiology 45, 14731484.
Creasey, A., Mendis, K., Carlton, J., Williamson, D., Wilson, I. and Carter, R. (1994). Maternal inheritance of extrachromosomal DNA in malaria parasites. Molecular and Biochemical Parasitology 65, 9598.
Day, K. P., Karamalis, F., Thompson, J., Barnes, D. A., Peterson, C., Brown, H., Brown, G. V. and Kemp, D. J. (1993). Genes necessary for expression of a virulence determinant and for transmission of Plasmodium falciparum are located on a 0.3-megabase region of chromosome 9. Proceedings of the National Academy of Sciences, USA 90, 82928296.
Delrieu, I., Waller, C. C., Mota, M. M., Grainger, M., Langhorne, J. and Holder, A. A. (2001). PSLAP, a protein with multiple adhesive motifs, is expressed in Plasmodium falciparum gametocytes. Molecular and Biochemical Parasitology 121, 1120.
Dessens, J. T., Beetsma, A. L., Dimopoulos, G., Wengelnik, K., Crisanti, A., Kafatos, F. C. and Sinden, R. E. (1999). CTRP is essential for mosquito infection by malaria ookinetes. EMBO Journal 18, 62216227.
Dessens, J. T., Mendoza, J., Claudianos, C., Vinetz, J. M., Khater, E., Hassard, S., Ranawaka, G. R. and Sinden, R. E. (2001). Knockout of the rodent malaria parasite chitinase pbCHT1 reduces infectivity to mosquitoes. Infection and Immunity 69, 40414047.
Dessens, J. T., Siden-Kiamos, I., Mendoza, J., Mahairaki, V., Khater, E., Vlachou, D., Xu, X. J., Kafatos, F. C., Louis, C., Dimopoulos, G. and Sinden, R. E. (2003). SOAP, a novel malaria ookinete protein involved in mosquito midgut invasion and oocyst development. Molecular Microbiology 49, 319329.
Dessens, J. T., Sinden, R. E. and Claudianos, C. (2004). LCCL proteins of apicomplexan parasites. Trends in Parasitology 20, 102108.
van Dijk, M. R., Douradinha, B., Franke-Fayard, B., Heussler, V., van Dooren, M. W., van Schaijk, B., van Gemert, G. J., Sauerwein, R. W., Mota, M. M., Waters, A. P. and Janse, C. J. (2005). Genetically attenuated, P36p-deficient malarial sporozoites induce protective immunity and apoptosis of infected liver cells. Proceedings of the National Academy of Sciences, USA 102, 1219412199.
van Dijk, M. R., Janse, C. J., Thompson, J., Waters, A. P., Braks, J. A., Dodemont, H. J., Stunnenberg, H. G., van Gemert, G. J., Sauerwein, R. W. and Eling, W. (2001). A central role for P48/45 in malaria parasite male gamete fertility. Cell 104, 153164.
Doerig, C. (2004). Protein kinases as targets for anti-parasitic chemotherapy. Biochimica et Biophysica Acta 1697, 155168.
Doerig, C., Billker, O., Pratt, D. and Endicott, J. (2005). Protein kinases as targets for antimalarial intervention: Kinomics, structure-based design, transmission-blockade, and targeting host cell enzymes. Biochimica et Biophysica Acta 1754, 132150.
Dorin, D., Alano, P., Boccaccio, I., Ciceron, L., Doerig, C., Sulpice, R., Parzy, D. and Doerig, C. (1999). An atypical mitogen-activated protein kinase (MAPK) homologue expressed in gametocytes of the human malaria parasite Plasmodium falciparum. Identification of a MAPK signature. Journal of Biological Chemistry 274, 2991229920.
Dorin, D., Le Roch, K., Sallicandro, P., Alano, P., Parzy, D., Poullet, P., Meijer, L. and Doerig, C. (2001). Pfnek-1, a NIMA-related kinase from the human malaria parasite Plasmodium falciparum Biochemical properties and possible involvement in MAPK regulation. European Journal of Biochemistry 268, 26002608.
Duffy, P. E. and Kaslow, D. C. (1997). A novel malaria protein, Pfs28, and Pfs25 are genetically linked and synergistic as falciparum malaria transmission-blocking vaccines. Infection and Immunity 65, 11091113.
Ecker, A., Pinto, S. B., Baker, K. W., Kafatos, F. C. and Sinden, R. E. (2007). Plasmodium berghei: Plasmodium perforin-like protein 5 is required for mosquito midgut invasion in Anopheles stephensi. Experimental Parasitology 116, 504508.
Eksi, S., Czesny, B., van Gemert, G. J., Sauerwein, R. W., Eling, W. and Williamson, K. C. (2006). Malaria transmission-blocking antigen, Pfs230, mediates human red blood cell binding to exflagellating male parasites and oocyst production. Molecular Microbiology 61, 991998.
Eksi, S., Czesny, B., van Gemert, G. J., Sauerwein, R. W., Eling, W. and Williamson, K. C. (2007). Inhibition of Plasmodium falciparum oocyst production by membrane-permeant cysteine protease inhibitor E64d. Antimicrobial Agents and Chemotherapy 51, 10641070.
Eksi, S., Czesny, B., Greenbaum, D. C., Bogyo, M. and Williamson, K. C. (2004). Targeted disruption of Plasmodium falciparum cysteine protease, falcipain 1, reduces oocyst production, not erythrocytic stage growth. Molecular Microbiology 53, 243250.
Eksi, S., Haile, Y., Furuya, T., Ma, L., Su, X. and Williamson, K. C. (2005). Identification of a subtelomeric gene family expressed during the asexual-sexual stage transition in Plasmodium falciparum. Molecular and Biochemical Parasitology 143, 9099.
Eksi, S. and Williamson, K. C. (2002). Male-specific expression of the paralog of malaria transmission-blocking target antigen Pfs230, PfB0400w. Molecular and Biochemical Parasitology 122, 127130.
Fanning, S. L., Czesny, B., Sedegah, M., Carucci, D. J., van Gemert, G. J., Eling, W. and Williamson, K. C. (2003). A glycosylphosphatidylinositol anchor signal sequence enhances the immunogenicity of a DNA vaccine encoding Plasmodium falciparum sexual-stage antigen, Pfs230. Vaccine 21, 32283325.
Feng, Z., Hoffmann, R. N., Nussenzweig, R. S., Tsuji, M., Fujioka, H., Aikawa, M., Lensen, T. H., Ponnudurai, T. and Pologe, L. G. (1993). Pfs2400 can mediate antibody-dependent malaria transmission inhibition and may be the Plasmodium falciparum 11.1 gene product. Journal of Experimental Medicine 177, 273281.
Florens, L., Washburn, M. P., Raine, J. D., Anthony, R. M., Grainger, M., Haynes, J. D., Moch, J. K., Muster, N., Sacci, J. B., Tabb, D. L., Witney, A. A., Wolters, D., Wu, Y., Gardner, M. J., Holder, A A., Sinden, R. E., Yates, J. R. and Carucci, D. J. (2002). A proteomic view of the Plasmodium falciparum life cycle. Nature, London 419, 520526.
Furuya, T., Mu, J., Hayton, K., Liu, A., Duan, J., Nkrumah, L., Joy, D. A., Fidock, D. A., Fujioka, H., Vaidya, A. B., Wellems, T. E. and Su, X. Z. (2005). Disruption of a Plasmodium falciparum gene linked to male sexual development causes early arrest in gametocytogenesis. Proceedings of the National Academy of Sciences, USA 102, 1681316818.
Garcia, G. E., Wirtz, R. A., Barr, J. R., Woolfitt, A. and Rosenberg, R. (1998). Xanthurenic acid induces gametogenesis in Plasmodium, the malaria parasite. Journal of Biological Chemistry 273, 1200312005.
Gardiner, D. L., Dixon, M. W., Spielmann, T., Skinner-Adams, T. S., Hawthorne, P. L., Ortega, M. R., Kemp, D. J. and Trenholme, K. R. (2005). Implication of a Plasmodium falciparum gene in the switch between asexual reproduction and gametocytogenesis. Molecular and Biochemical Parasitology 140, 153160.
Gardner, M. J., Hall, N., Fung, E., White, O., Berriman, M., Hyman, R. W., Carlton, J. M., Pain, A., Nelson, K. E., Bowman, S., Paulsen, I. T., James, K., Eisen, J. A., Rutherford, K., Salzberg, S. L., Craig, A., Kyes, S., Chan, M. S., Nene, V., Shallom, S. J., Suh, B., Peterson, J., Angiuoli, S., Pertea, M., Allen, J., Selengut, J., Haft, D., Mather, M. W., Vaidya, A. B., Martin, D. M., Fairlamb, A. H., Fraunholz, M. J., Roos, D. S., Ralph, S. A., McFadden, G. I., Cummings, L. M., Subramanian, G. M., Mungall, C., Venter, J. C., Carucci, D. J., Hoffman, S. L., Newbold, C., Davis, R. W., Fraser, C. M. and Barrell, B. (2002). Genome sequence of the human malaria parasite Plasmodium falciparum. Nature, London 419, 498511.
Gerloff, D. L., Creasey, A., Maslau, S. and Carter, R. (2005). Structural models for the protein family characterized by gamete surface protein Pfs230 of Plasmodium falciparum. Proceedings of the National Academy of Sciences, USA 102, 1359813603.
Gwadz, R. W. (1976). Successful immunization against the sexual stages of Plasmodium gallinaceum. Science 193, 11501151.
Haddad, D., Maciel, J. and Kumar, N. (2006). Infection with Plasmodium berghei boosts antibody responses primed by a DNA vaccine encoding gametocyte antigen Pbs48/45. Infection and Immunity 74, 20432051.
Hall, N., Karras, M., Raine, J. D., Carlton, J. M., Kooij, T. W., Berriman, M., Florens, L., Janssen, C. S., Pain, A., Christophides, G. K., James, K., Rutherford, K., Harris, B., Harris, D., Churcher, C., Quail, M. A., Ormond, D., Doggett, J., Trueman, H. E., Mendoza, J., Bidwell, S. L., Rajandream, M. A., Carucci, D. J., Yates, J. R. 3rd, Kafatos, F. C., Janse, C. J., Barrell, B., Turner, C. M., Waters, A. P. and Sinden, R. E. (2005). A comprehensive survey of the Plasmodium life cycle by genomic, transcriptomic, and proteomic analyses. Science 307, 8286.
Hawking, F., Wilson, M. E. and Gammage, K. (1971). Evidence for cyclic development and short-lived maturity in the gametocytes of Plasmodium falciparum. Transactions of the Royal Society of Tropical Medicine and Hygiene 65, 549559.
Healer, J., McGuinness, D., Carter, R. and Riley, E. (1999). Transmission-blocking immunity to Plasmodium falciparum in malaria-immune individuals is associated with antibodies to the gamete surface protein Pfs230. Parasitology 119, 425433.
Hirai, M., Arai, M., Kawai, S. and Matsuoka, H. (2006). PbGCbeta is essential for Plasmodium ookinete motility to invade midgut cell and for successful completion of parasite life cycle in mosquitoes. Journal of Biochemistry (Tokyo) 140, 747757.
Hisaeda, H., Stowers, A. W., Tsuboi, T., Collins, W. E., Sattabongkot, J. S., Suwanabun, N., Torii, M. and Kaslow, D. C. (2000). Antibodies to malaria vaccine candidates Pvs25 and Pvs28 completely block the ability of Plasmodium vivax to infect mosquitoes. Infection and Immunity 68, 66186623.
Ishino, T., Orito, Y., Chinzei, Y. and Yuda, M. (2006). A calcium-dependent protein kinase regulates Plasmodium ookinete access to the midgut epithelial cell. Molecular Microbiology 59, 11751184.
Janse, C. J., van der Klooster, P. F., van der Kaay, H. J., van der Ploeg, M. and Overdulve, J. P. (1986). DNA synthesis in Plasmodium berghei during asexual and sexual development. Molecular and Biochemical Parasitology 20, 173182.
Janse, C. J., Ponnudurai, T., Lensen, A. H., Meuwissen, J. H., Ramesar, J., van der Ploeg, M. and Overdulve, J. P. (1988). DNA synthesis in gametocytes of Plasmodium falciparum. Parasitology 96, 17.
Kadota, K., Ishino, T., Matsuyama, T., Chinzei, Y. and Yuda, M. (2004). Essential role of membrane-attack protein in malarial transmission to mosquito host. Proceedings of the National Academy of Sciences, USA 101, 1631016315.
Kariu, T., Ishino, T., Yano, K., Chinzei, Y. and Yuda, M. (2006). CelTOS, a novel malarial protein that mediates transmission to mosquito and vertebrate host. Molecular Microbiology 59, 13691379.
Kaslow, D. C. (2002). Transmission-blocking vaccines. Chemical Immunology 80, 287307.
Kaslow, D. C., Quakyi, I. A., Syin, C., Raum, M. G., Keister, D. B., Coligan, J. E., McCutchan, T. F. and Miller, L. H. (1988). A vaccine candidate from the sexual stage of human malaria that contains EGF-like domains. Nature, London 333, 7476.
Kawamoto, F., Alejo-Blanco, R., Fleck, S. L., Kawamoto, Y. and Sinden, R. E. (1990). Possible roles of Ca2+ and cGMP as mediators of the exflagellation of Plasmodium berghei and Plasmodium falciparum. Molecular and Biochemical Parasitology 42, 101108.
Kawamoto, F., Fujioka, H., Murakami, R., Syafruddin, , Hagiwara, M., Ishikawa, T. and Hidaka, H. (1993). The roles of Ca2+/calmodiulin- and cGMP-dependent pathways in gametognesis of a rodent malaria parasite, Plasmodium berghei. European Journal of Cell Biology 60, 101107.
Khan, S. M., Franke-Fayard, B., Mair, G. R., Lasonder, E., Janse, C. J., Mann, M. and Waters, A. P. (2005). Proteome analysis of separated male and female gametocytes reveals novel sex-specific Plasmodium biology. Cell 121, 675687.
Kongkasuriyachai, D., Fujioka, H. and Kumar, N. (2004). Functional analysis of Plasmodium falciparum parasitophorous vacuole membrane protein (Pfs16) during gametocytogenesis and gametogenesis by targeted gene disruption. Molecular and Biochemical Parasitology 133, 275285.
Kumar, N. (1987). Target antigens of malaria transmission blocking immunity exist as a stable membrane bound complex. Parasite Immunology 9, 321335.
Kumar, N. (1997). Protein phosphorylation during sexual differentiation in the malaria parasite Plasmodium falciparum. Molecular and Biochemical Parasitology 87, 205210.
Kumar, N. and Wizel, B. (1992). Further characterization of interactions between gamete surface antigens of Plasmodium falciparum. Molecular and Biochemical Parasitology 53, 113120.
Lanfrancotti, A., Bertuccini, L., Silvestrini, F. and Alano, P. (2007). Plasmodium falciparum: mRNA co-expression and protein co-localisation of two gene products upregulated in early gametocytes. Experimental Parasitology 116, 497503.
Langer, R. C., Hayward, R E., Tsuboi, T., Tachibana, M., Torii, M. and Vinetz, J. M. (2000). Micronemal transport of Plasmodium ookinete chitinases to the electron-dense area of the apical complex for extracellular secretion. Infection and Immunity 68, 64616465.
Lasonder, E., Ishihama, Y., Andersen, J. S., Vermunt, A. M., Pain, A., Sauerwein, R. W., Eling, W. M., Hall, N., Waters, A. P., Stunnenberg, H. G. and Mann, M. (2002). Analysis of the Plasmodium falciparum proteome by high-accuracy mass spectrometry. Nature, London 419, 537542.
Lavazec, C., Bonnet, S., Thiery, I., Boisson, B. and Bourgouin, C. (2005). cpbAg1 encodes an active carboxypeptidase B expressed in the midgut of Anopheles gambiae. Insect Molecular Biology 14, 163174.
Lavazec, C., Boudin, C., Lacroix, R., Bonnet, S., Diop, A., Thiberge, S., Boisson, B., Tahar, R. and Bourgouin, C. (2007). Carboxypeptidases B of Anopheles gambiae as targets for a Plasmodium falciparum transmission-blocking vaccine. Infection and Immunity 75, 16351642.
Lensen, A., Bril, A., van de Vegte, M., van Gemert, G. J., Eling, W. and Sauerwein, R. (1999). Plasmodium falciparum: infectivity of cultured, synchronized gametocytes to mosquitoes. Experimental Parasitology 91, 101103.
Li, F., Templeton, T. J., Popov, V., Comer, J. E., Tsuboi, T., Torii, M. and Vinetz, J. M. (2004). Plasmodium ookinete-secreted proteins secreted through a common micronemal pathway are targets of blocking malaria transmission. Journal of Biological Chemistry 279, 2663526644.
Li, F., Patra, K. P. and Vinetz, J. M. (2005). An anti-chitinase malaria transmission-blocking single-chain antibody as an effector molecule for creating a Plasmodium falciparum-refractory mosquito. Journal of Infection and Diseases 192, 878887.
Linares, G. E. and Rodriguez, J. B. (2007). Current status and progresses made in malaria chemotherapy. Current Medicinal Chemistry 14, 289314.
Lobo, C. A., Konings, P. N.& H. and Kumar, N. (1994). Expression of early gametocyte-stage antigens Pfg27 and Pfs16 in synchronized gametocytes and non-gametocyte producing clones of Plasmodium falciparum. Molecular and Biochemical Parasitology 68, 151154.
Lobo, C. A., Fujioka, H., Aikawa, M. and Kumar, N. (1999). Disruption of the Pfg27 locus by homologous recombination leads to loss of the sexual phenotype in P. falciparum. Molecular Cell 3, 793798.
Lye, Y. M., Chan, M. and Sim, T. S. (2006). Pfnek3: an atypical activator of a MAP kinase in Plasmodium falciparum. FEBS Letters 580, 60836092.
Mair, G. R., Braks, J. A., Garver, L. S., Wiegant, J. C., Hall, N., Dirks, R. W., Khan, S. M., Dimopoulos, G., Janse, C. J. and Waters, A. P. (2006). Regulation of sexual development of Plasmodium by translational repression. Science 313, 667669.
Malkin, E M., Durbin, A. P., Diemert, D. J., Sattabongkot, J., Wu, Y., Miura, K., Long, C. A., Lambert, L., Miles, A..P, Wang, J., Stowers, A., Miller, L. H. and Saul, A. (2005). Phase 1 vaccine trial of Pvs25H: a transmission blocking vaccine for Plasmodium vivax malaria. Vaccine 23, 31313138.
Martin, S. K., Jett, M. and Schneider, I. (1994). Correlation of phosphoinositide hydrolysis with exflagellation in the malaria microgametocyte. Journal of Parasitology 180, 371378.
Moelans, I. I., Meis, J. F., Kocken, C., Konings, R. N. and Schoenmakers, J. G. (1991). A novel protein antigen of malaria parasite Plasmodium falciparum, located on the surface of gametes and sporozoites. Molecular and Biochemical Parasitology 45, 193204.
Muhia, D. K., Swales, C. A., Deng, W., Kelly, J. M. and Baker, D. A. (2001). The gametocyte-activating factor xanthurenic acid stimulates an increase in membrane-associated guanylyl cyclase activity in the human malaria parasite Plasmodium falciparum. Molecular Microbiology 42, 553560.
Nijhout, M. M. (1979). Plasmodium gallinaceum: exflagellation stimulated by a mosquito factor. Experimental Parasitology 148, 7580.
Nijhout, M. M. and Carter, R. (1978). Gamete development in malaria parasites: bicarbonate-dependent stimulation by pH in vitro. Parasitology 76, 3953.
O'Donnell, R. A. and Blackman, M. J. (2005). The role of malaria merozoite proteases in red blood cell invasion. Current Opinion in Microbiology 8, 422427.
Outchkourov, N., Vermunt, A., Jansen, J., Kaan, A., Roeffen, W., Teelen, K., Lasonder, E., Braks, A., van de Vegte-Bolmer, M., Qiu, L. Y., Sauerwein, R. and Stunnenberg, H. G. (2007). Epitope analysis of the malaria surface antigen PFS48/45 identifies a subdomain that elicits transmission blocking antibodies. Journal of Biological Chemistry 282, 1714817156.
Pace, T., Olivieri, A., Sanchez, M., Albanesi, V., Picci, L., Siden Kiamos, I., Janse, C. J., Waters, A. P., Pizzi, E. and Ponzi, M. (2006). Set regulation in asexual and sexual Plasmodium parasites reveals a novel mechanism of stage-specific expression. Molecular Microbiology 60, 870882.
Pradel, G. and Templeton, T. J. (2005). Genomics of pathogenic parasites. In Pathogenomics – Genome Analysis of Pathogenic Microbes (ed. Dobrindt, U. and Hacker, J. H.), pp. 417444. Wiley-VCH, Weinheim, Germany.
Pradel, G., Hayton, K., Aravind, L., Iyer, L., Abrahamsen, M. S., Bonawitz, A., Mejia, C. and Templeton, T. J. (2004). A multi-domain adhesion protein family expressed in Plasmodium falciparum gametocytes is essential for sporozoite midgut to salivary gland transition. Journal of Experimental Medicine 199, 15331544.
Pradel, G., Wagner, C., Mejia, C. and Templeton, T. J. (2006). Plasmodium falciparum: Co-dependent expression and co-localization of the PfCCp multi-adhesion domain proteins. Experimental Parasitology 112, 263268.
Quakyi, I. A., Carter, R., Rener, J., Kumar, N., Good, M. F. and Miller, L. H. (1987). The 230-kDa gamete surface protein of Plasmodium falciparum is also a target for transmission-blocking antibodies. Journal of Immunology 139, 42134217.
Raine, J. D., Ecker, A., Mendoza, J., Tewari, R., Stanway, R. R. and Sinden, R. E. (2007). Female inheritance of malarial lap genes is essential for mosquito transmission. PLoS Pathogen 3, e30.
Rangarajan, R., Bei, A. K., Jethwaney, D., Maldonado, P., Dorin, D., Sultan, A. A. and Doerig, C. (2005). A mitogen-activated protein kinase regulates male gametogenesis and transmission of the malaria parasite Plasmodium berghei. EMBO Report 6, 464469.
Rawlings, D. J., Fujioka, H., Fried, M., Keister, D. B., Aikawa, M. and Kaslow, D. C. (1992). Alpha-tubulin II is a male-specific protein in Plasmodium falciparum. Molecular and Biochemical Parasitology 56, 239250.
Read, D., Lensen, A. H., Begarnie, S., Haley, S., Raza, A. and Carter, R. (1994). Transmission-blocking antibodies against multiple, non-variant target epitopes of the Plasmodium falciparum gamete surface antigen Pfs230 are all complement-fixing. Parasite Immunology 16, 5115151159.
Reininger, L., Billker, O., Tewari, R., Mukhopadhyay, A., Fennell, C., Dorin-Semblat, D., Doerig, C., Goldring, D., Harmse, L., Ranford-Cartwright, L., Packer, J. and Doerig, C. (2005). A NIMA-related protein kinase is essential for completion of the sexual cycle of malaria parasites. Journal of Biological Chemistry 280, 19571964.
Rener, J., Graves, P. M., Carter, R., Williams, J. L. and Burkot, T. R. (1983). Target antigens of transmission blocking immunity on gametes of Plasmodium falciparum. Journal of Experimental Medicine 158, 976981.
Rodriguez, M. DEL C., Martinez-Barnetche, J., Alvarado-Delgado, A., Batista, C., Argotte-Ramos, R. S., Hernandez-Martinez, S., Gonzalez Ceron, L., Torres, J. A., Margos, G. and Rodriguez, M. H. (2007). The surface protein Pvs25 of Plasmodium vivax ookinetes interacts with calreticulin on the midgut apical surface of the malaria vector Anopheles albimanus. Molecular and Biochemical Parasitology 153, 167177.
Rogers, N. J., Hall, B. S., Obiero, J., Targets, G. A.& T. and Sutherland, C. J. (2000). A model for sequestration of the transmission stages of Plasmodium falciparum: Adhesion of gametocyte-infected erythrocytes to human bone marrow cells. Infection and Immunity 68, 34553462.
Rosenthal, P. J. (2002). Hydrolysis of erythrocyte proteins by proteases of malaria parasites. Current Opinion in Hematology 9, 140145.
Rosenthal, P. J. (2004). Cysteine proteases of malaria parasites. International Journal for Parasitology 34, 14891499.
Sargeant, T. J., Marti, M., Caler, E., Carlton, J. M., Simpson, K., Speed, T. P. and Cowman, A. F. (2006). Lineage-specific expansion of proteins exported to erythrocytes in malaria parasites. Genome Biology 7, R12.
van Schaijk, B. C.& L., van Dijk, M. R., van de Vegte-Bolmer, M., van Gemert, G.-J., van Dooren, M. W., Eksi, S., Roeffen, W. F.& G., Janse, C. J., Waters, A. P. and Sauerwein, R. W. (2006). Pfs47, paralog of the male fertility factor Pfs48/45, is a female specific surface protein in Plasmodium falciparum. Molecular and Biochemical Parasitology 149, 216222.
Scherf, A., Carter, R., Petersen, C., Alano, P., Nelson, R., Aikawa, M., Mattei, D., Pereira da Silva, L. and Leech, J. (1992). Gene inactivation of Pf11–1 of Plasmodium falciparum by chromosome breakage and healing: identification of a gametocyte-specific protein with a potential role in gametogenesis. EMBO Journal 11, 22932301.
Severini, C., Silvestrini, F., Sannella, A., Barca, S., Gradoni, L. and Alano, P. (1999). The production of the osmiophilic body protein Pfg377 is associated with stage of maturation and sex in Plasmodium falciparum gametocytes. Molecular and Biochemical Parasitology 100, 247252.
Sharma, A., Sharma, I., Kogkasuriyachai, D. and Kumar, N. (2003). Structure of a gametocyte protein essential for sexual development in Plasmodium falciparum. Nature Structural Biology 10, 197203.
Siden-Kiamos, I., Ecker, A., Nyback, S., Louis, C., Sinden, R. E. and Billker, O. (2006). Plasmodium berghei calcium-dependent protein kinase 3 is required for ookinete gliding motility and mosquito midgut invasion. Molecular Microbiology 60, 13551363.
Silvestrini, F., Alano, P. and Williams, J. L. (2000). Commitment to the production of male and female gametocytes in the human malaria parasite Plasmodium falciparum. Parasitology 121, 465471.
Silvestrini, F., Bozdech, Z., Lanfrancotti, A., Di Giulio, E., Bultrini, E., Picci, L., deRisi, J. L., Pizzi, E. and Alano, P. (2005). Genome-wide identification of genes upregulated at the onset of gametocytogenesis in Plasmodium falciparum. Molecular and Biochemical Parasitology 143, 100110.
Sinden, R. E. (1982). Gametocytogenesis of Plasmodium falciparum in vitro: an electron microscopic study. Parasitology 84, 111.
Sinden, R. E., Canning, E. U., Bray, R. S. and Smalley, M. E. (1978). Gametocyte and gamete development in Plasmodium falciparum. Proceedings of the Royal Society of London, B 375399.
Sinden, R. E., Canning, E. U. and Spain, B. (1976). Gametogenesis and fertilization in Plasmodium yoelii nigeriensis: a transmission electron microscope study. Proceedings of the Royal Society of London, B 193, 5576.
Smalley, M. E., Abdalla, S. and Brown, J. (1980). The distribution of Plasmodium falciparum in the peripheral blood and bone marrow of Gambian children. Transactions of the Royal Society of Tropical Medicine and Hygiene 75, 103105.
Smalley, M. E. and Sinden, R. E. (1977). Plasmodium falciparum gametocytes: their longevity and infectivity. Parasitology 74, 18.
Smith, T. G., Lourenco, P., Carter, R., Walliker, D. and Ranford-Cartwright, L. C. (2000). Commitment to sexual differentiation in the human malaria parasite, Plasmodium falciparum. Parasitology 121, 127133.
Stowers, A. and Carter, R. (2001). Current developments in malaria transmission-blocking vaccines. Expert Opinion on Biological Therapy 1, 619628.
Talman, A. M., Domarle, O., McKenzie, F. E., Ariey, F. and Robert, V. (2004). Gametocytogenesis: the puberty of Plasmodium falciparum. Malaria Journal 3, 24.
Templeton, T. J., Iyer, L. M., Anantharaman, V., Enomoto, S., Abrahante, J. E., Subramanian, G. M., Hoffman, S. L., Abrahamsen, M. S. and Aravind, L. (2004). Comparative analysis of apicomplexa and genomic diversity in eukaryotes. Genome Research 14, 16861695.
Templeton, T. J. and Kaslow, D. C. (1999). Identification of additional members define a Plasmodium falciparum gene superfamily which includes Pfs48/45 and Pfs230. Molecular and Biochemical Parasitology 101, 223227.
Templeton, T. J., Kaslow, D. C. and Fidock, D. A. (2000). Developmental arrest of the human malaria parasite Plasmodium falciparum within the mosquito midgut via CTRP gene disruption. Molecular Microbiology 36, 19.
Templeton, T. J., Keister, D. B., Muratova, O., Procter, J. L. and Kaslow, D. C. (1998). Adherence of erythrocytes during exflagellation of Plasmodium falciparum microgametes is dependent on erythrocyte surface sialic acid and glycophorins. Journal of Experimental Medicine 187, 15991609.
Tewari, R., Dorin, D., Moon, R., Doerig, C. and Billker, O. (2005). An atypical mitogen-activated protein kinase controls cytokinesis and flagellar motility during male gamete formation in a malaria parasite. Molecular Microbiology 58, 12531263.
Thomson, J. G. and Robertson, A. (1935). The structure and development of Plasmodium falciparum gametocytes in the internal organs and in the peripheral circulation. Transactions of the Royal Society of Tropical Medicine and Hygiene 29, 3140.
Tomas, A. M., Margos, G., Dimopoulos, G., van Lin, L. H., de Koning-Ward, T. F., Sinha, R., Lupetti, P., Beetsma, A. L., Rodriguez, M. C., Karras, M., Hager, A., Mendoza, J., Butcher, G. A., Kafatos, F., Janse, C. J., Waters, A P. and Sinden, R. E. (2001). P25 and P28 proteins of the malaria ookinete surface have multiple and partially redundant functions. EMBO Journal 20, 39753983.
Torres, J. A., Rodriguez, M. H., Rodriguez, M. C. and de la Cruz Hernandez-Hernandez, F. (2005). Plasmodium berghei: Effect of protease inhibitors during gametogenesis and early zygote development. Experimental Parasitology 111, 255259.
Tosini, F., Agnoli, A., Mele, R., Moralez, M. A.& G. and Pozio, E. (2004). A new modular protein of Cryptosporidium parvum, with ricin B and LCCL domains, expressed in the sporozoite invasive stage. Molecular and Biochemical Parasitology 134, 137147.
Trottein, F., Triglia, T. and Cowman, A. F. (1995). Molecular cloning of a gene from Plasmodium falciparum that codes for a protein sharing motifs found in adhesive molecules from mammals and Plasmodia. Molecular and Biochemical Parasitology 74, 129141.
Trueman, H. E., Raine, J. D., Florens, L., Dessens, J. T., Mendoza, J., Johnson, J., Waller, C. C., Delrieu, I., Holders, A. A., Langhorne, J., Carucci, D. J., Yates, J. R. 3rd and Sinden, R. E. (2004). Functional characterization of an LCCL-lectin domain containing protein family in Plasmodium berghei. Journal of Parasitology 90, 10621071.
Tsai, Y. L., Hayward, R. E., Langer, R. C., Fidock, D. A. and Vinetz, J. M. (2001). Disruption of Plasmodium falciparum chitinase markedly impairs parasite invasion of mosquito midgut. Infection and Immunity 69, 40484054.
Vaidya, A. B., Morrisey, J., Plowe, C. V., Kaslow, D. C. and Wellems, T. E. (1993). Unidirectional dominance of cytoplasmic inheritance in two genetic crosses of Plasmodium falciparum. Molecular and Cellular Biology 13, 73497357.
Vaughan, J. A., Noden, B. H. and Beier, J. C. (1994). Sporogonic development of cultured Plasmodium falciparum in six species of laboratory-reared Anopheles mosquitoes. American Journal of Tropical Medicine and Hygiene 51, 233243.
Vermeulen, A. N., Ponnudurai, T., Beckers, P. J.& A., Verhave, J. P., Smits, M. A. and Meuwissen, J. H. (1985). Sequential expression of antigens on sexual stages of Plasmodium falciparum accessible to transmission blocking antibodies in the mosquito. Journal of Experimental Medicine 162, 14601476.
Vermeulen, A. N., Van Deursen, J., Brakenhoff, R. H., Lensen, T. H.& W., Ponnudurai, T. and Meuwissen, J. H. (1986). Characterisation of Plasmodium falciparum sexual stage antigens and their biosynthesis in synchronised gametocyte cultures. Molecular and Biochemical Parasitology 20, 155163.
Vinetz, J. M., Dave, S. K., Specht, C. A., Brameld, K. A., Xu, B., Hayward, R. and Fidock, D. A. (1999). The chitinase PfCHT1 from the human malaria parasite Plasmodium falciparum lacks proenzyme and chitin-binding domains and displays unique substrate preferences. Proceedings of the National Academy of Sciences, USA 96, 1406114066.
Vinetz, J. M., Valenzuela, J. G., Specht, C. A., Aravind, L., Langer, R. C., Ribeiro, J. M. and Kaslow, D. C. (2000). Chitinases of the avian malaria parasite Plasmodium gallinaceum, a class of enzymes necessary for parasite invasion of the mosquito midgut. Journal of Biological Chemistry 275, 1033110341.
Wagner, C., Scholz, S. M., Abreu, A., Frank, R., Templeton, T. J. and Pradel, G. (2006). Molecular interactions between PfCCp multidomain adhesion proteins during gametogenesis in Plasmodium falciparum. Proceedings of the ICOPA XI meeting, Medimond 631635.
Ward, P., Equinet, L., Packer, J. and Doerig, C. (2004). Protein kinases of the human malaria parasite Plasmodium falciparum: the kinome of a divergent eukaryote. BMC Genomics 5, 79.
Williamson, K. C. (2003). Pfs230: from malaria transmission-blocking vaccine candidate toward function. Parasite Immunology 25, 351359.
Williamson, K. C., Criscio, M. D. and Kaslow, D. C. (1993). Cloning and expression of the gene for Plasmodium falciparum transmission-blocking target antigen Pfs230. Molecular and Biochemical Parasitology 58, 355358.
Williamson, K. C., Fujioka, H., Aikawa, M. and Kaslow, D. C. (1996). Stage-specific processing of Pfs230, a Plasmodium falciparum transmission-blocking vaccine candidate. Molecular and Biochemical Parasitology 78, 161169.
Williamson, K. C., Keister, D. B., Muratova, O. and Kaslow, D. C. (1995). Recombinant Pfs230, a Plasmodium falciparum gametocyte protein, induces antisera that reduce the infectivity of Plasmodium falciparum to mosquitoes. Molecular and Bochemical Parasitology 75, 3342.
Wu, Y., Wang, X., Liu, X. and Wang, Y. (2003). Data-mining approaches reveal hidden families of proteases in the genome of malaria parasite. Genome Research 13, 601616.
Yuda, M., Sawai, T. and Chinzei, Y. (1999). Structure and expression of an adhesive protein-like molecule of mosquito invasive-stage malarial parasite. Journal of Experimental Medicine 189, 19471952.
Yuda, M., Yano, K., Tsuboi, T., Torii, M. and Chinzei, Y. (2001). Von Willebrand Factor A domain-related protein, a novel microneme protein of the malaria ookinete highly conserved throughout Plasmodium parasites. Molecular and Biochemical Parasitology 116, 6572.


Related content

Powered by UNSILO

Proteins of the malaria parasite sexual stages: expression, function and potential for transmission blocking strategies

  • G. PRADEL (a1)


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.