Hostname: page-component-8448b6f56d-dnltx Total loading time: 0 Render date: 2024-04-16T20:20:25.431Z Has data issue: false hasContentIssue false

Protein trafficking in Plasmodium falciparum-infected red cells and impact of the expansion of exported protein families

Published online by Cambridge University Press:  30 July 2014

SURENDRA K. PRAJAPATI*
Affiliation:
Molecular Biology Division, National Institute of Malaria Research, New Delhi, India
RICHARD CULLETON
Affiliation:
Malaria Unit, Institute for Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan
OM P. SINGH
Affiliation:
Molecular Biology Division, National Institute of Malaria Research, New Delhi, India
*
*Corresponding author: Molecular Biology Division, National Institute of Malaria Research, New Delhi, India. E-mail: surendramrc@gmail.com

Summary

Erythrocytes are extensively remodelled by the malaria parasite following invasion of the cell. Plasmodium falciparum encodes numerous virulence-associated and host-cell remodelling proteins that are trafficked to the cytoplasm, the cell membrane and the surface of the infected erythrocyte. The export of soluble proteins relies on a sequence directing entry into the secretory pathways in addition to an export signal. The export signal consisting of five amino acids is termed the Plasmodium export element (PEXEL) or the vacuole transport signal (VTS). Genome mining studies have revealed that PEXEL/VTS carrying protein families have expanded dramatically in P. falciparum compared with other malaria parasite species, possibly due to lineage-specific expansion linked to the unique requirements of P. falciparum for host-cell remodelling. The functional characterization of such genes and gene families may reveal potential drug targets that could inhibit protein trafficking in infected erythrocytes. This review highlights some of the recent advances and key knowledge gaps in protein trafficking pathways in P. falciparum-infected red cells and speculates on the impact of exported gene families in the trafficking pathway.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2014 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Acharya, P., Kumar, R. and Tatu, U. (2007). Chaperoning a cellular upheaval in malaria: heat shock proteins in Plasmodium falciparum. Molecular and Biochemical Parasitology 153, 8594. doi: 10.1016/j.molbiopara.2007.01.009.Google Scholar
Acharya, P., Chaubey, S., Grover, M. and Tatu, U. (2012). An exported heat shock protein 40 associates with pathogenesis-related knobs in Plasmodium falciparum infected erythrocytes. PLoS ONE 7, e44605. doi: 10.1371/journal.pone.0044605.Google Scholar
Alexandre, J. S., Yahata, K., Kawai, S., Torii, M. and Kaneko, O. (2011). PEXEL-independent trafficking of Plasmodium falciparum SURFIN4.2 to the parasite-infected red blood cell and Maurer's clefts. Parasitology International 60, 313320. doi: 10.1016/j.parint.2011.05.003.Google Scholar
Andrade, B. B., Reis-Filho, A., Souza-Neto, S. M., Clarencio, J., Camargo, L. M., Barral, A. and Barral-Netto, M. (2010). Severe Plasmodium vivax malaria exhibits marked inflammatory imbalance. Malaria Journal 9, 13. doi: 10.1186/1475-2875-9-13.Google Scholar
Ansorge, I., Benting, J., Bhakdi, S. and Lingelbach, K. (1996). Protein sorting in Plasmodium falciparum-infected red blood cells permeabilized with the pore-forming protein streptolysin O. Biochemical Journal 315, 307314.Google Scholar
Bernabeu, M., Lopez, F. J., Ferrer, M., Martin-Jaular, L., Razaname, A., Corradin, G., Maier, A. G., Del Portillo, H. A. and Fernandez-Becerra, C. (2012). Functional analysis of Plasmodium vivax VIR proteins reveals different subcellular localizations and cytoadherence to the ICAM-1 endothelial receptor. Cellular Microbiology 14, 386400. doi: 10.1111/j.1462-5822.2011.01726.x.Google Scholar
Bhattacharjee, S., van Ooij, C., Balu, B., Adams, J. H. and Haldar, K. (2008). Maurer's clefts of Plasmodium falciparum are secretory organelles that concentrate virulence protein reporters for delivery to the host erythrocyte. Blood 111, 24182426. doi: 10.1182/blood-2007-09-115279.Google Scholar
Bhattacharjee, S., Stahelin, R. V., Speicher, K. D., Speicher, D. W. and Haldar, K. (2012). Endoplasmic reticulum PI(3)P lipid binding targets malaria proteins to the host cell. Cell 148, 201212. doi: 10.1016/j.cell.2011.10.051.Google Scholar
Blisnick, T., Morales Betoulle, M. E., Barale, J. C., Uzureau, P., Berry, L., Desroses, S., Fujioka, H., Mattei, D. and Braun Breton, C. (2000). Pfsbp1, a Maurer's cleft Plasmodium falciparum protein, is associated with the erythrocyte skeleton. Molecular and Biochemical Parasitology 111, 107121. doi: 10.1016/S0166-6851(00)00301-7.Google Scholar
Boddey, J. A., Moritz, R. L., Simpson, R. J. and Cowman, A. F. (2009). Role of the Plasmodium export element in trafficking parasite proteins to the infected erythrocyte. Traffic 10, 285299. doi: 10.1111/j.1600-0854.2008.00864.x.Google Scholar
Boddey, J. A., Hodder, A. N., Gunther, S., Gilson, P. R., Patsiouras, H., Kapp, E. A., Pearce, J. A., de Koning-Ward, T. F., Simpson, R. J., Crabb, B. S. and Cowman, A. F. (2010). An aspartyl protease directs malaria effector proteins to the host cell. Nature 463, 627631. doi: 10.1038/nature08728.Google Scholar
Boddey, J. A., Carvalho, T. G., Hodder, A. N., Sargeant, T. J., Sleebs, B. E., Marapana, D., Lopaticki, S., Nebl, T. and Cowman, A. F. (2013). Role of plasmepsin V in export of diverse protein families from the Plasmodium falciparum exportome. Traffic 14, 532550. doi: 10.1111/tra.12053.CrossRefGoogle ScholarPubMed
Bullen, H. E., Charnaud, S. C., Kalanon, M., Riglar, D. T., Dekiwadia, C., Kangwanrangsan, N., Torii, M., Tsuboi, T., Baum, J., Ralph, S. A., Cowman, A. F., de Koning-Ward, T. F., Crabb, B. S. and Gilson, P. R. (2012). Biosynthesis, localization, and macromolecular arrangement of the Plasmodium falciparum translocon of exported proteins (PTEX). Journal of Biological Chemistry 287, 78717884. doi: 10.1074/jbc.M111.328591.Google Scholar
Chang, H. H., Falick, A. M., Carlton, P. M., Sedat, J. W., DeRisi, J. L. and Marletta, M. A. (2008). N-terminal processing of proteins exported by malaria parasites. Molecular and Biochemical Parasitology 160, 107115. doi: 10.1016/j.molbiopara.2008.04.011.Google Scholar
Cooke, B. M., Lingelbach, K., Bannister, L. H. and Tilley, L. (2004). Protein trafficking in Plasmodium falciparum-infected red blood cells. Trends in Parasitology 20, 581589. doi: 10.1016/j.pt.2004.09.008.Google Scholar
Decherf, G., Egee, S., Staines, H. M., Ellory, J. C. and Thomas, S. L. (2004). Anionic channels in malaria-infected human red blood cells. Blood Cells, Molecules and Diseases 32, 366371. doi: 10.1016/j.bcmd.2004.01.008.Google Scholar
de Koning-Ward, T. F., Gilson, P. R., Boddey, J. A., Rug, M., Smith, B. J., Papenfuss, A. T., Sanders, P. R., Lundie, R. J., Maier, A. G., Cowman, A. F. and Crabb, B. S. (2009). A newly discovered protein export machine in malaria parasites. Nature 459, 945949. doi: 10.1038/nature08104.Google Scholar
Desai, S. A., Bezrukov, S. M. and Zimmerberg, J. (2000). A voltage-dependent channel involved in nutrient uptake by red blood cells infected with the malaria parasite. Nature 406, 10011005. doi: 10.1038/35023000.Google Scholar
Diez-Silva, M., Park, Y., Huang, S., Bow, H., Mercereau-Puijalon, O., Deplaine, G., Lavazec, C., Perrot, S., Bonnefoy, S., Feld, M. S., Han, J., Dao, M. and Suresh, S. (2012). Pf155/RESA protein influences the dynamic microcirculatory behavior of ring-stage Plasmodium falciparum infected red blood cells. Scientific Reports 2, 614. doi: 10.1038/srep00614.Google Scholar
Dixon, M. W., Hawthorne, P. L., Spielmann, T., Anderson, K. L., Trenholme, K. R. and Gardiner, D. L. (2008). Targeting of the ring exported protein 1 to the Maurer's clefts is mediated by a two-phase process. Traffic 9, 13161326. doi: 10.1111/j.1600-0854.2008.00768.x.Google Scholar
Dzikowski, R., Frank, M. and Deitsch, K. (2006 a). Mutually exclusive expression of virulence genes by malaria parasites is regulated independently of antigen production. PLoS Pathology 2, e22. doi: 10.1371/journal.ppat.0020022.Google Scholar
Dzikowski, R., Templeton, T. J. and Deitsch, K. (2006 b). Variant antigen gene expression in malaria. Cellular Microbiology 8, 13711381. doi: 10.1111/j.1462-5822.2006.00760.x.Google Scholar
Favaloro, J. M., Coppel, R. L., Corcoran, L. M., Foote, S. J., Brown, G. V., Anders, R. F. and Kemp, D. J. (1986). Structure of the RESA gene of Plasmodium falciparum. Nucleic Acids Research 14, 82658277.CrossRefGoogle ScholarPubMed
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 419, 520526. doi: 10.1038/nature01107.Google Scholar
Florens, L., Liu, X., Wang, Y., Yang, S., Schwartz, O., Peglar, M., Carucci, D. J., Yates, J. R. III and Wub, Y. (2004). Proteomics approach reveals novel proteins on the surface of malaria-infected erythrocytes. Molecular and Biochemical Parasitology 135, 111.Google Scholar
Foley, M. and Tilley, L. (1998). Protein trafficking in malaria-infected erythrocytes. International Journal of Parasitology 28, 16711680.Google Scholar
Gehde, N., Hinrichs, C., Montilla, I., Charpian, S., Lingelbach, K. and Przyborski, J. M. (2009). Protein unfolding is an essential requirement for transport across the parasitophorous vacuolar membrane of Plasmodium falciparum. Molecular Microbiology 71, 613628. doi: 10.1111/j.1365-2958.2008.06552.x.Google Scholar
Glenister, F. K., Coppel, R. L., Cowman, A. F., Mohandas, N. and Cooke, B. M. (2002). Contribution of parasite proteins to altered mechanical properties of malaria-infected red blood cells. Blood 99, 10601063.CrossRefGoogle ScholarPubMed
Gormley, J. A., Howard, R. J. and Taraschi, T. F. (1992). Trafficking of malarial proteins to the host cell cytoplasm and erythrocyte surface membrane involves multiple pathways. Journal of Cell Biology 119, 14811495.Google Scholar
Haase, S., Herrmann, S., Gruring, C., Heiber, A., Jansen, P. W., Langer, C., Treeck, M., Cabrera, A., Bruns, C., Struck, N. S., Kono, M., Engelberg, K., Ruch, U., Stunnenberg, H. G., Gilberger, T. W. and Spielmann, T. (2009). Sequence requirements for the export of the Plasmodium falciparum Maurer's clefts protein REX2. Molecular Microbiology 71, 10031017. doi: 10.1111/j.1365-2958.2008.06582.x.Google Scholar
Hawthorne, P. L., Trenholme, K. R., Skinner-Adams, T. S., Spielmann, T., Fischer, K., Dixon, M. W., Ortega, M. R., Anderson, K. L., Kemp, D. J. and Gardiner, D. L. (2004). A novel Plasmodium falciparum ring stage protein, REX, is located in Maurer's clefts. Molecular and Biochemical Parasitology 136, 181189.Google Scholar
Hiller, N. L., Bhattacharjee, S., van Ooij, C., Liolios, K., Harrison, T., Lopez-Estrano, C. and Haldar, K. (2004). A host-targeting signal in virulence proteins reveals a secretome in malarial infection. Science 306, 19341937. doi: 10.1126/science.1102737.Google Scholar
Hodder, A. N., Maier, A. G., Rug, M., Brown, M., Hommel, M., Pantic, I., Puig-de-Morales-Marinkovic, M., Smith, B., Triglia, T., Beeson, J. and Cowman, A. F. (2009). Analysis of structure and function of the giant protein Pf332 in Plasmodium falciparum. Molecular Microbiology 71, 4865. doi: 10.1111/j.1365-2958.2008.06508.x.Google Scholar
Klemba, M. and Goldberg, D. E. (2005). Characterization of plasmepsin V, a membrane-bound aspartic protease homolog in the endoplasmic reticulum of Plasmodium falciparum. Molecular and Biochemical Parasitology 143, 183191. doi: 10.1016/j.molbiopara.2005.05.015.Google Scholar
Kochar, D. K., Saxena, V., Singh, N., Kochar, S. K., Kumar, S. V. and Das, A. (2005). Plasmodium vivax malaria. Emerging Infectious Diseases 11, 132134. doi: 10.3201/eid1101.040519.Google Scholar
Lanzer, M., Wickert, H., Krohne, G., Vincensini, L. and Braun Breton, C. (2006). Maurer's clefts: a novel multi-functional organelle in the cytoplasm of Plasmodium falciparum-infected erythrocytes. International Journal of Parasitology 36, 2336. doi: 10.1016/j.ijpara.2005.10.001.Google Scholar
Lopez, F. J., Bernabeu, M., Fernandez-Becerra, C. and del Portillo, H. A. (2013). A new computational approach redefines the subtelomeric vir superfamily of Plasmodium vivax. BMC Genomics 14, 8. doi: 10.1186/1471-2164-14-8.Google Scholar
Maier, A. G., Rug, M., O'Neill, M. T., Beeson, J. G., Marti, M., Reeder, J. and Cowman, A. F. (2007). Skeleton-binding protein 1 functions at the parasitophorous vacuole membrane to traffic PfEMP1 to the Plasmodium falciparum-infected erythrocyte surface. Blood 109, 12891297. doi: 10.1182/blood-2006-08-043364.Google Scholar
Maier, A. G., Rug, M., O'Neill, M. T., Brown, M., Chakravorty, S., Szestak, T., Chesson, J., Wu, Y., Hughes, K., Coppel, R. L., Newbold, C., Beeson, J. G., Craig, A., Crabb, B. S. and Cowman, A. F. (2008). Exported proteins required for virulence and rigidity of Plasmodium falciparum-infected human erythrocytes. Cell 134, 4861. doi: 10.1016/j.cell.2008.04.051.Google Scholar
Marti, M., Good, R. T., Rug, M., Knuepfer, E. and Cowman, A. F. (2004). Targeting malaria virulence and remodeling proteins to the host erythrocyte. Science 306, 19301933. doi: 10.1126/science.1102452.Google Scholar
Matthews, K., Kalanon, M., Chisholm, S. A., Sturm, A., Goodman, C. D., Dixon, M. W., Sanders, P. R., Nebl, T., Fraser, F., Haase, S., McFadden, G. I., Gilson, P. R., Crabb, B. S. and de Koning-Ward, T. F. (2013). The Plasmodium translocon of exported proteins (PTEX) component thioredoxin-2 is important for maintaining normal blood-stage growth. Molecular Microbiology 89, 11671186. doi: 10.1111/mmi.12334.Google Scholar
Mayer, C., Slater, L., Erat, M. C., Konrat, R. and Vakonakis, I. (2012). Structural analysis of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) intracellular domain reveals a conserved interaction epitope. Journal of Biological Chemistry 287, 71827189. doi: 10.1074/jbc.M111.330779.Google Scholar
Mendis, K., Sina, B. J., Marchesini, P. and Carter, R. (2001). The neglected burden of Plasmodium vivax malaria. American Journal of Tropical Medicine and Hygiene 64(1–2 Suppl.), 97106.Google Scholar
Merino, E. F., Fernandez-Becerra, C., Durham, A. M., Ferreira, J. E., Tumilasci, V. F., d'Arc-Neves, J., da Silva-Nunes, M., Ferreira, M. U., Wickramarachchi, T., Udagama-Randeniya, P., Handunnetti, S. M. and Del Portillo, H. A. (2006). Multi-character population study of the vir subtelomeric multigene superfamily of Plasmodium vivax, a major human malaria parasite. Molecular and Biochemical Parasitology 149, 1016. doi: 10.1016/j.molbiopara.2006.04.002.Google Scholar
Miller, L. H., Good, M. F. and Milon, G. (1994). Malaria pathogenesis. Science 264, 18781883.Google Scholar
Nyalwidhe, J. and Lingelbach, K. (2006). Proteases and chaperones are the most abundant proteins in the parasitophorous vacuole of Plasmodium falciparum-infected erythrocytes. Proteomics 6, 15631573. doi: 10.1002/pmic.200500379.Google Scholar
Pick, C., Ebersberger, I., Spielmann, T., Bruchhaus, I. and Burmester, T. (2011). Phylogenomic analyses of malaria parasites and evolution of their exported proteins. BMC Evolutionary Biology 11, 167. doi: 10.1186/1471-2148-11-167.Google Scholar
Raventos-Suarez, C., Kaul, D. K., Macaluso, F. and Nagel, R. L. (1985). Membrane knobs are required for the microcirculatory obstruction induced by Plasmodium falciparum-infected erythrocytes. Proceedings of the National Academy of Sciences USA 82, 38293833.Google Scholar
Riglar, D. T., Rogers, K. L., Hanssen, E., Turnbull, L., Bullen, H. E., Charnaud, S. C., Przyborski, J., Gilson, P. R., Whitchurch, C. B., Crabb, B. S., Baum, J. and Cowman, A. F. (2013). Spatial association with PTEX complexes defines regions for effector export into Plasmodium falciparum-infected erythrocytes. Nature Communications 4, 1415. doi: 10.1038/ncomms2449.Google Scholar
Rogerson, S. J. and Carter, R. (2008). Severe vivax malaria: newly recognised or rediscovered. PLoS Medicine 5, e136. doi: 10.1371/journal.pmed.0050136.CrossRefGoogle ScholarPubMed
Russo, I., Babbitt, S., Muralidharan, V., Butler, T., Oksman, A. and Goldberg, D. E. (2010). Plasmepsin V licenses Plasmodium proteins for export into the host erythrocyte. Nature 463, 632636. doi: 10.1038/nature08726.Google Scholar
Salanti, A., Dahlback, M., Turner, L., Nielsen, M. A., Barfod, L., Magistrado, P., Jensen, A. T., Lavstsen, T., Ofori, M. F., Marsh, K., Hviid, L. and Theander, T. G. (2004). Evidence for the involvement of VAR2CSA in pregnancy-associated malaria. Journal of Experimental Medicine 200, 11971203. doi: 10.1084/jem.20041579.Google Scholar
Saliba, K. J., Horner, H. A. and Kirk, K. (1998). Transport and metabolism of the essential vitamin pantothenic acid in human erythrocytes infected with the malaria parasite Plasmodium falciparum. Journal of Biological Chemistry 273, 1019010195.Google Scholar
Sam-Yellowe, T. Y. (2009). The role of the Maurer's clefts in protein transport in Plasmodium falciparum. Trends in Parasitology 25, 277284. doi: 10.1016/j.pt.2009.03.009.Google Scholar
Sam-Yellowe, T. Y., Florens, L., Johnson, J. R., Wang, T., Drazba, J. A., Le Roch, K. G., Zhou, Y., Batalov, S., Carucci, D. J., Winzeler, E. A. and Yates, J. R. III (2004). A Plasmodium gene family encoding Maurer's cleft membrane proteins: structural properties and expression profiling. Genome Research 14, 10521059. doi: 10.1101/gr.2126104.Google Scholar
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. doi: 10.1186/gb-2006-7-2-r12.Google Scholar
Saridaki, T., Sanchez, C. P., Pfahler, J. and Lanzer, M. (2008). A conditional export system provides new insights into protein export in Plasmodium falciparum-infected erythrocytes. Cellular Microbiology 10, 24832495. doi: 10.1111/j.1462-5822.2008.01223.x.Google Scholar
Saridaki, T., Frohlich, K. S., Braun-Breton, C. and Lanzer, M. (2009). Export of PfSBP1 to the Plasmodium falciparum Maurer's clefts. Traffic 10, 137152. doi: 10.1111/j.1600-0854.2008.00860.x.Google Scholar
Schatz, G. and Dobberstein, B. (1996). Common principles of protein translocation across membranes. Science 271, 15191526.Google Scholar
Schnell, D. J. and Hebert, D. N. (2003). Protein translocons: multifunctional mediators of protein translocation across membranes. Cell 112, 491505. doi: 10.1016/S0092-8674(03)00110-7.Google Scholar
Shonhai, A., Boshoff, A. and Blatch, G. L. (2007). The structural and functional diversity of Hsp70 proteins from Plasmodium falciparum. Protein Science 16, 18031818. doi: 10.1110/ps.072918107.Google Scholar
Sijwali, P. S. and Rosenthal, P. J. (2010). Functional evaluation of Plasmodium export signals in Plasmodium berghei suggests multiple modes of protein export. PLoS ONE 5, e10227. doi: 10.1371/journal.pone.0010227.Google Scholar
Snow, R. W., Guerra, C. A., Noor, A. M., Myint, H. Y. and Hay, S. I. (2005). The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature 434, 214217. doi: 10.1038/nature03342.Google Scholar
Spielmann, T. and Gilberger, T. W. (2010). Protein export in malaria parasites: do multiple export motifs add up to multiple export pathways? Trends in Parasitology 26, 610. doi: 10.1016/j.pt.2009.10.001.Google Scholar
Spielmann, T., Hawthorne, P. L., Dixon, M. W., Hannemann, M., Klotz, K., Kemp, D. J., Klonis, N., Tilley, L., Trenholme, K. R. and Gardiner, D. L. (2006). A cluster of ring stage-specific genes linked to a locus implicated in cytoadherence in Plasmodium falciparum codes for PEXEL-negative and PEXEL-positive proteins exported into the host cell. Molecular Biology of the Cell 17, 36133624. doi: 10.1091/mbc.E06-04-0291.Google Scholar
Spycher, C., Klonis, N., Spielmann, T., Kump, E., Steiger, S., Tilley, L. and Beck, H. P. (2003). MAHRP-1, a novel Plasmodium falciparum histidine-rich protein, binds ferriprotoporphyrin IX and localizes to the Maurer's clefts. Journal of Biological Chemistry 278, 3537335383. doi: 10.1074/jbc.M305851200.Google Scholar
Spycher, C., Rug, M., Klonis, N., Ferguson, D. J., Cowman, A. F., Beck, H. P. and Tilley, L. (2006). Genesis of and trafficking to the Maurer's clefts of Plasmodium falciparum-infected erythrocytes. Molecular and Cellular Biology 26, 40744085. doi: 10.1128/MCB.00095-06.Google Scholar
Staines, H. M., Powell, T., Thomas, S. L. and Ellory, J. C. (2004). Plasmodium falciparum-induced channels. International Journal of Parasitology 34, 665673. doi: 10.1016/j.ijpara.2004.02.007.Google Scholar
Staines, H. M., Alkhalil, A., Allen, R. J., De Jonge, H. R., Derbyshire, E., Egee, S., Ginsburg, H., Hill, D. A., Huber, S. M., Kirk, K., Lang, F., Lisk, G., Oteng, E., Pillai, A. D., Rayavara, K., Rouhani, S., Saliba, K. J., Shen, C., Solomon, T., Thomas, S. L., Verloo, P. and Desai, S. A. (2007). Electrophysiological studies of malaria parasite-infected erythrocytes: current status. International Journal of Parasitology 37, 475482. doi: 10.1016/j.ijpara.2006.12.013.Google Scholar
Suwanarusk, R., Chavchich, M., Russell, B., Jaidee, A., Chalfein, F., Barends, M., Prasetyorini, B., Kenangalem, E., Piera, K. A., Lek-Uthai, U., Anstey, N. M., Tjitra, E., Nosten, F., Cheng, Q. and Price, R. N. (2008). Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax. Journal of Infectious Diseases 198, 15581564. doi: 10.1086/592451.Google Scholar
Taraschi, T. F., Trelka, D., Martinez, S., Schneider, T. and O'Donnell, M. E. (2001). Vesicle-mediated trafficking of parasite proteins to the host cell cytosol and erythrocyte surface membrane in Plasmodium falciparum infected erythrocytes. International Journal of Parasitology 31, 13811391. doi: 10.1016/S0020-7519(01)00256-9.Google Scholar
Taraschi, T. F., O'Donnell, M., Martinez, S., Schneider, T., Trelka, D., Fowler, V. M., Tilley, L. and Moriyama, Y. (2003). Generation of an erythrocyte vesicle transport system by Plasmodium falciparum malaria parasites. Blood 102, 34203426. doi: 10.1182/blood-2003-05-1448 2003-05-1448.Google Scholar
ter Kuile, F. O. and Rogerson, S. J. (2008). Plasmodium vivax infection during pregnancy: an important problem in need of new solutions. Clinical Infectious Diseases 46, 13821384. doi: 10.1086/586744.Google Scholar
Tilley, L., Sougrat, R., Lithgow, T. and Hanssen, E. (2008). The twists and turns of Maurer's cleft trafficking in P. falciparum-infected erythrocytes. Traffic 9, 187197. doi: 10.1111/j.1600-0854.2007.00684.x.Google Scholar
Tjitra, E., Anstey, N. M., Sugiarto, P., Warikar, N., Kenangalem, E., Karyana, M., Lampah, D. A. and Price, R. N. (2008). Multidrug-resistant Plasmodium vivax associated with severe and fatal malaria: a prospective study in Papua, Indonesia. PLoS Medicine 5, e128. doi: 10.1371/journal.pmed.0050128.Google Scholar
Trelka, D. P., Schneider, T. G., Reeder, J. C. and Taraschi, T. F. (2000). Evidence for vesicle-mediated trafficking of parasite proteins to the host cell cytosol and erythrocyte surface membrane in Plasmodium falciparum infected erythrocytes. Molecular and Biochemical Parasitology 106, 131145. doi: 10.1016/S0166-6851(99)00207-8.Google Scholar
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. doi: 10.1186/1471-2164-5-79.Google Scholar
Waterkeyn, J. G., Wickham, M. E., Davern, K. M., Cooke, B. M., Coppel, R. L., Reeder, J. C., Culvenor, J. G., Waller, R. F. and Cowman, A. F. (2000). Targeted mutagenesis of Plasmodium falciparum erythrocyte membrane protein 3 (PfEMP3) disrupts cytoadherence of malaria-infected red blood cells. EMBO Journal 19, 28132823. doi: 10.1093/emboj/19.12.2813.Google Scholar
Wickert, H. and Krohne, G. (2007). The complex morphology of Maurer's clefts: from discovery to three-dimensional reconstructions. Trends in Parasitology 23, 502509. doi: 10.1016/j.pt.2007.08.008.Google Scholar
Winter, G., Kawai, S., Haeggstrom, M., Kaneko, O., von Euler, A., Kawazu, S., Palm, D., Fernandez, V. and Wahlgren, M. (2005). SURFIN is a polymorphic antigen expressed on Plasmodium falciparum merozoites and infected erythrocytes. Journal of Experimental Medicine 201, 18531863. doi: 10.1084/jem.20041392.Google Scholar