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Role of the Plasmodium Export Element in Trafficking Parasite Proteins to the Infected Erythrocyte
Justin A Boddey, Robert L Moritz, Richard J Simpson and 1 more
Traffic · 2009
doi:10.1111/j.1600-0854.2008.00864.x
Abstract
The intracellular survival of Plasmodium falciparum within human erythrocytes is dependent on export of parasite proteins that remodel the host cell. Most exported proteins require a conserved motif (RxLxE/Q/D), termed the Plasmodium export element (PEXEL) or vacuolar targeting sequence (VTS), for targeting beyond the parasitophorous vacuole membrane and into the host cell; however, the precise role of this motif in export is poorly defined. We used transgenic P. falciparum expressing chimeric proteins to investigate the function of the PEXEL motif for export. The PEXEL constitutes a bifunctional export motif comprising a protease recognition sequence that is cleaved, in the endoplasmic reticulum, from proteins destined for export, in a PEXEL arginine‐ and leucine‐dependent manner. Following processing, the remaining conserved PEXEL residue is required to direct the mature protein to the host cell. Furthermore, we demonstrate that N acetylation of proteins following N‐terminal processing is a PEXEL‐independent process that is insufficient for correct export to the host cell. This work defines the role of each residue in the PEXEL for export into the P. falciparum ‐infected erythrocyte.
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References 49
- 1.
Snow RW, Guerra CA, Noor AM, Myint HY, Hay SI. The global distribution of clinical episodes of Plasmodium falciparum malaria. Nature. 2005;434:214-217.
Not in our library10.1038/nature03342
- 2.
Marti M, Baum J, Rug M, Tilley L, Cowman AF. Signal-mediated export of proteins from the malaria parasite to the host erythrocyte. J Cell Biol. 2005;171:587-592.
Not in our library10.1083/jcb.200508051
- 3.
Smith JD, Chitnis CE, Craig AG, Roberts DJ, Hudson-Taylor DE, Peterson DS, Pinches R, Newbold CI, Miller LH. Switches in expression of Plasmodium falciparum var genes correlate with changes in antigenic and cytoadherent phenotypes of infected erythrocytes. Cell. 1995;82:101-110.
Not in our library10.1016/0092-8674(95)90056-x
- 4.
Baruch DI, Pasloske BL, Singh HB, Bi X, Ma XC, Feldman M, Taraschi TF, Howard RJ. Cloning the P.falciparum gene encoding PfEMP1, a malarial variant antigen and adherence receptor on the surface of parasitized human erythrocytes. Cell. 1995;82:77-87.
Not in our library10.1016/0092-8674(95)90054-3
- 5.
Su X-Z, Kirkman LA, Fujioka H, Wellems TE. Complex polymorphisms in an ∼330 kDa protein are linked to chloroquine-resistant P. falciparum in Southeast Asia and Africa. Cell. 1997;91:593-603.
Not in our library10.1016/s0092-8674(00)80447-x
- 6.
Kraemer SM, Smith JD. A family affair: var genes, PfEMP1 binding, and malaria disease. Curr Opin Microbiol. 2006;9:374-380.
Not in our library10.1016/j.mib.2006.06.006
- 7.
Wickham ME, Rug M, Ralph SA, Klonis N, McFadden GI, Tilley L, Cowman AF. Trafficking and assembly of the cytoadherence complex in Plasmodium falciparum-infected human erythrocytes. EMBO J. 2001;20:1-14.
Not in our library10.1093/emboj/20.20.5636
- 8.
Lopez-Estrano C, Bhattacharjee S, Harrison T, Haldar K. Cooperative domains define a unique host cell-targeting signal in Plasmodium falciparum-infected erythrocytes. Proc Natl Acad Sci USA. 2003;100:12402-12407.
Not in our library10.1073/pnas.2133080100
- 9.
Kriek N, Tilley L, Horrocks P, Pinches R, Elford BC, Ferguson DJ, Lingelbach K, Newbold CI. Characterization of the pathway for transport of the cytoadherence-mediating protein, PfEMP1, to the host cell surface in malaria parasite-infected erythrocytes. Mol Microbiol. 2003;50:1215-1227.
Not in our library10.1046/j.1365-2958.2003.03784.x
- 10.
Papakrivos J, Newbold CI, Lingelbach K. A potential novel mechanism for the insertion of a membrane protein revealed by a biochemical analysis of the Plasmodium falciparum cytoadherence molecule PfEMP-1. Mol Microbiol. 2005;55:1272-1284.
Not in our library10.1111/j.1365-2958.2004.04468.x
- 11.
Knuepfer E, Rug M, Klonis N, Tilley L, Cowman AF. Trafficking of the major virulence factor to the surface of transfected P. falciparum-infected erythrocytes. Blood. 2005;105:4078-4087.
Not in our library10.1182/blood-2004-12-4666
- 12.
Cooke BM, Buckingham DW, Glenister FK, Fernandez KM, Bannister LH, Marti M, Mohandas N, Coppel RL. A Maurer's cleft-associated protein is essential for expression of the major malaria virulence antigen on the surface of infected red blood cells. J Cell Biol. 2006;172:899-908.
Not in our library10.1083/jcb.200509122
- 13.
Maier AG, Rug M, O'Neill MT, Beeson JG, Marti M, Reeder J, Cowman AF. Skeleton-binding protein 1 functions at the parasitophorous vacuole membrane to traffic PfEMP1 to the Plasmodium falciparum-infected erythrocyte surface. Blood. 2007;109:1289-1297.
Not in our library10.1182/blood-2006-08-043364
- 14.
- 15.
Spycher C, Rug M, Pachlatko E, Hanssen E, Ferguson D, Cowman AF, Tilley L, Beck HP. The Maurer's cleft protein MAHRP1 is essential for trafficking of PfEMP1 to the surface of Plasmodium falciparum-infected erythrocytes. Mol Microbiol. 2008;68:1300-1314.
Not in our library10.1111/j.1365-2958.2008.06235.x
- 16.
Baumeister S, Winterberg M, Duranton C, Huber SM, Lang F, Kirk K, Lingelbach K. Evidence for the involvement of Plasmodium falciparum proteins in the formation of new permeability pathways in the erythrocyte membrane. Mol Microbiol. 2006;60:493-504.
Not in our library10.1111/j.1365-2958.2006.05112.x
- 17.
Crabb BS, Cooke BM, Reeder JC, Waller RF, Caruana SR, Davern KM, Wickham ME, Brown GV, Coppel RL, Cowman AF. Targeted gene disruption shows that knobs enable malaria-infected red cells to cytoadhere under physiological shear stress. Cell. 1997;89:287-296.
Not in our library10.1016/s0092-8674(00)80207-x
- 18.
Glenister FK, Coppel RL, Cowman AF, Mohandas N, Cooke BM. Contribution of parasite proteins to altered mechanical properties of malaria-infected red blood cells. Blood. 2002;99:1060-1063.
Not in our library10.1182/blood.v99.3.1060
- 19.
Marti M, Good RT, Rug M, Knuepfer E, Cowman AF. Targeting malaria virulence and remodeling proteins to the host erythrocyte. Science. 2004;306:1930-1933.
Not in our library10.1126/science.1102452
- 20.
Hiller NL, Bhattacharjee S, van Ooij C, Liolios K, Harrison T, Lopez-Estrano C, Haldar K. A host-targeting signal in virulence proteins reveals a secretome in malarial infection. Science. 2004;306:1934-1937.
Not in our library10.1126/science.1102737
- 21.
Singh AP, Buscaglia CA, Wang Q, Levay A, Nussenzweig DR, Walker JR, Winzeler EA, Fujii H, Fontoura BM, Nussenzweig V. Plasmodium circumsporozoite protein promotes the development of the liver stages of the parasite. Cell. 2007;131:492-504.
Not in our library10.1016/j.cell.2007.09.013
- 22.
- 23.
Ravetch JV, Kochan J, Perkins M. Isolation of the gene for a glycophorin-binding protein implicated in erythrocyte invasion by a malaria parasite. Science. 1985;227:1593-1597.
Not in our library10.1126/science.3883491
- 24.
Chang HH, Falick AM, Carlton PM, Sedat JW, DeRisi JL, Marletta MA. N-terminal processing of proteins exported by malaria parasites. Mol Biochem Parasitol. 2008;160:107-115.
Not in our library10.1016/j.molbiopara.2008.04.011
- 25.
Hiller NL, Akompong T, Morrow JS, Holder AA, Haldar K. Identification of a stomatin orthologue in vacuoles induced in human erythrocytes by malaria parasites. J Biol Chem. 2003;278:48413-48421.
Not in our library10.1074/jbc.m307266200
- 26.
Fischer K, Marti T, Rick B, Johnson D, Benting J, Baumeister S, Helmbrecht C, Lanzer M, Lingelbach K. Characterization and cloning of the gene encoding the vacuolar membrane protein EXP-2 from Plasmodium falciparum. Mol Biochem Parasitol. 1998;92:47-57.
Not in our library10.1016/s0166-6851(97)00224-7
- 27.
La Greca N, Hibbs AR, Riffkin C, Foley M, Tilley L. Identification of an endoplasmic reticulum-resident calcium-binding protein with multiple EF-hand motifs in asexual stages of Plasmodium falciparum. Mol Biochem Parasitol. 1997;89:283-293.
Not in our library10.1016/s0166-6851(97)00134-5
- 28.
Wiek S, Cowman AF, Lingelbach K. Double cross-over gene replacement within the sec 7 domain of a GDP-GTP exchange factor from Plasmodium falciparum allows the generation of a transgenic brefeldin A-resistant parasite line. Mol Biochem Parasitol. 2004;138:51-55.
Not in our library10.1016/j.molbiopara.2004.06.015
- 29.
Lingelbach K, Przyborski JM. The long and winding road: protein trafficking mechanisms in the Plasmodium falciparum infected erythrocyte. Mol Biochem Parasitol. 2006;147:1-8.
Not in our library10.1016/j.molbiopara.2006.01.014
- 30.
Waller RF, Reed MB, Cowman AF, McFadden GI. Protein trafficking to the plastid of Plasmodium falciparum is via the secretory pathway. EMBO J. 2000;19:1794-1802.
Not in our library10.1093/emboj/19.8.1794
- 31.
Przyborski JM, Miller SK, Pfahler JM, Henrich PP, Rohrbach P, Crabb BS, Lanzer M. Trafficking of STEVOR to the Maurer's clefts in Plasmodium falciparum-infected erythrocytes. EMBO J. 2005;24:2306-2317.
Not in our library10.1038/sj.emboj.7600720
- 32.
Saridaki T, Sanchez CP, Pfahler J, Lanzer M. A conditional export system provides new insights into protein export in Plasmodium falciparum-infected erythrocytes. Cell Microbiol. 2008;10:2483-2495.
Not in our library10.1111/j.1462-5822.2008.01223.x
- 33.
Bendtsen JD, Nielsen H, von Heijne G, Brunak S. Improved prediction of signal peptides: SignalP 3.0. J Mol Biol. 2004;340:783-795.
Not in our library10.1016/j.jmb.2004.05.028
- 34.
Lippincott-Schwartz J, Roberts TH, Hirschberg K. Secretory protein trafficking and organelle dynamics in living cells. Annu Rev Cell Dev Biol. 2000;16:557-589.
Not in our library10.1146/annurev.cellbio.16.1.557
- 35.
Sato K, Nakano A. Mechanisms of COPII vesicle formation and protein sorting. FEBS Lett. 2007;581:2076-2082.
Not in our library10.1016/j.febslet.2007.01.091
- 36.
Martinez-Menarguez JA, Geuze HJ, Slot JW, Klumperman J. Vesicular tubular clusters between the ER and Golgi mediate concentration of soluble secretory proteins by exclusion from COPI-coated vesicles. Cell. 1999;98:81-90.
Not in our library10.1016/s0092-8674(00)80608-x
- 37.
Albano FR, Berman A, La Greca N, Hibbs AR, Wickham M, Foley M, Tilley L. A homologue of SAR1p localises to a novel trafficking pathway in malaria-infected erythrocytes. Eur J Cell Biol. 1999;78:453-462.
Not in our library10.1016/s0171-9335(99)80072-7
- 38.
Wickert H, Wissing F, Andrews KT, Stich A, Krohne G, Lanzer M. Evidence for trafficking of PfEMP1 to the surface of P. falciparum-infected erythrocytes via a complex membrane network. Eur J Cell Biol. 2003;82:271-284.
Not in our library10.1078/0171-9335-00319
- 39.
Struck NS, Herrmann S, Schmuck-Barkmann I, de Souza Dias S, Haase S, Cabrera AL, Treeck M, Bruns C, Langer C, Cowman AF, Marti M, Spielmann T, Gilberger TW. Spatial dissection of the cis- and trans-Golgi compartments in the malaria parasite Plasmodium falciparum. Mol Microbiol. 2008;67:1320-1330.
Not in our library10.1111/j.1365-2958.2008.06125.x
- 40.
Adisa A, Frankland S, Rug M, Jackson K, Maier AG, Walsh P, Lithgow T, Klonis N, Gilson PR, Cowman AF, Tilley L. Re-assessing the locations of components of the classical vesicle-mediated trafficking machinery in transfected Plasmodium falciparum. Int J Parasitol. 2007;37:1127-1141.
Not in our library10.1016/j.ijpara.2007.02.009
Cited by papers we hold 4
- A revised mechanism for how Plasmodium falciparum recruits and exports proteins into its erythrocytic host cell. · 2022Not checked
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