Stable Translocation Intermediates Jam Global Protein Export in Plasmodium falciparum Parasites and Link the PTEX Component EXP2 with Translocation Activity

PLoS Pathogens

Volumn 12, Issue 5, 2016, Pages

  Mesén Ramírez, Paolo ^a   Reinsch, Ferdinand ^a   Blancke Soares, Alexandra ^a   Bergmann, Bärbel ^a   Ullrich, Ann Katrin ^a   Tenzer, Stefan ^b   Spielmann, Tobias ^a  

^a BERNHARD NOCHT INSTITUTE FOR TROPICAL MEDICINE   (Germany)

^b UNIVERSITY MEDICAL CENTER MAINZ   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

DIHYDROFOLATE REDUCTASE; MEMBRANE PROTEIN; PROTOZOAL PROTEIN;

ARTICLE; CELL MEMBRANE; CONCEPTUAL FRAMEWORK; CONTROLLED STUDY; GENE TRANSLOCATION; IMMUNOFLUORESCENCE TEST; IMMUNOPRECIPITATION; MASS SPECTROMETRY; NONHUMAN; PLASMODIUM FALCIPARUM; POLYMERASE CHAIN REACTION; PROTEOMICS; SEQUENCE ANALYSIS; SIGNAL TRANSDUCTION; WESTERN BLOTTING; ERYTHROCYTE; FLUORESCENT ANTIBODY TECHNIQUE; HUMAN; MALARIA FALCIPARUM; METABOLISM; PARASITOLOGY; PHYSIOLOGY; PROTEIN TRANSPORT;

BLOTTING, WESTERN; ERYTHROCYTES; FLUORESCENT ANTIBODY TECHNIQUE; HUMANS; IMMUNOPRECIPITATION; MALARIA, FALCIPARUM; PLASMODIUM FALCIPARUM; PROTEIN TRANSPORT; PROTOZOAN PROTEINS;

EID: 84973325983     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1005618     Document Type: Article

References (57)

1. WHO (2013) World Malaria Report. Geneva: World Health Organization.
2. Milner DA, Jr.Lee JJ, Frantzreb C, Whitten RO, Kamiza S, et al. (2015) Quantitative Assessment of Multiorgan Sequestration of Parasites in Fatal Pediatric Cerebral Malaria. J Infect Dis.
3. Spillman NJ, Beck JR, Goldberg DE, (2015) Protein export into malaria parasite-infected erythrocytes: mechanisms and functional consequences. Annu Rev Biochem84: 813–841. doi: 10.1146/annurev-biochem-060614-03415725621510
4. Marti M, Good RT, Rug M, Knuepfer E, Cowman AF, (2004) Targeting malaria virulence and remodeling proteins to the host erythrocyte. Science306: 1930–1933. 15591202
5. Hiller NL, Bhattacharjee S, van Ooij C, Liolios K, Harrison T, et al. (2004) A host-targeting signal in virulence proteins reveals a secretome in malarial infection. Science306: 1934–1937. 15591203
6. Boddey JA, Cowman AF, (2013) Plasmodium nesting: remaking the erythrocyte from the inside out. Annu Rev Microbiol67: 243–269. doi: 10.1146/annurev-micro-092412-15573023808341
7. Heiber A, Kruse F, Pick C, Gruring C, Flemming S, et al. (2013) Identification of new PNEPs indicates a substantial non-PEXEL exportome and underpins common features in Plasmodium falciparum protein export. PLoS Pathog9: e1003546. doi: 10.1371/journal.ppat.100354623950716
8. Spielmann T, Gilberger TW, (2010) Protein export in malaria parasites: do multiple export motifs add up to multiple export pathways?Trends Parasitol26: 6–10. doi: 10.1016/j.pt.2009.10.00119879191
9. Gruring C, Heiber A, Kruse F, Flemming S, Franci G, et al. (2012) Uncovering common principles in protein export of malaria parasites. Cell Host Microbe12: 717–729. doi: 10.1016/j.chom.2012.09.01023159060
10. Beck JR, Muralidharan V, Oksman A, Goldberg DE, (2014) PTEX component HSP101 mediates export of diverse malaria effectors into host erythrocytes. Nature511: 592–595. doi: 10.1038/nature1357425043010
11. Elsworth B, Matthews K, Nie CQ, Kalanon M, Charnaud SC, et al. (2014) PTEX is an essential nexus for protein export in malaria parasites. Nature511: 587–591. doi: 10.1038/nature1355525043043
12. Spielmann T, Montagna GN, Hecht L, Matuschewski K, (2012) Molecular make-up of the Plasmodium parasitophorous vacuolar membrane. Int J Med Microbiol302: 179–186. doi: 10.1016/j.ijmm.2012.07.01122898489
13. de Koning-Ward TF, Gilson PR, Boddey JA, Rug M, Smith BJ, et al. (2009) A newly discovered protein export machine in malaria parasites. Nature459: 945–949. doi: 10.1038/nature0810419536257
14. Gold DA, Kaplan AD, Lis A, Bett GC, Rosowski EE, et al. (2015) The Toxoplasma Dense Granule Proteins GRA17 and GRA23 Mediate the Movement of Small Molecules between the Host and the Parasitophorous Vacuole. Cell Host Microbe17: 642–652. doi: 10.1016/j.chom.2015.04.00325974303
15. Kalanon M, Bargieri D, Sturm A, Matthews K, Ghosh S, et al. (2015) The PTEX component EXP2 is critical for establishing a patent malaria infection in mice. Cell Microbiol.
16. Matz JM, Goosmann C, Brinkmann V, Grutzke J, Ingmundson A, et al. (2015) The Plasmodium berghei translocon of exported proteins reveals spatiotemporal dynamics of tubular extensions. Sci Rep5: 12532. doi: 10.1038/srep1253226219962
17. Spielmann T, Gilberger TW, (2015) Critical Steps in Protein Export of Plasmodium falciparum Blood Stages. Trends Parasitol31: 514–525. doi: 10.1016/j.pt.2015.06.01026433254
18. Deponte M, Hoppe HC, Lee MC, Maier AG, Richard D, et al. (2012) Wherever I may roam: protein and membrane trafficking in P. falciparum-infected red blood cells. Mol Biochem Parasitol186: 95–116. doi: 10.1016/j.molbiopara.2012.09.00723043991
19. Eilers M, Schatz G, (1986) Binding of a specific ligand inhibits import of a purified precursor protein into mitochondria. Nature322: 228–232. 3016548
20. Vestweber D, Schatz G, (1988) A chimeric mitochondrial precursor protein with internal disulfide bridges blocks import of authentic precursors into mitochondria and allows quantitation of import sites. J Cell Biol107: 2037–2043. 2904445
21. Gehde N, Hinrichs C, Montilla I, Charpian S, Lingelbach K, et al. (2009) Protein unfolding is an essential requirement for transport across the parasitophorous vacuolar membrane of Plasmodium falciparum. Mol Microbiol71: 613–628. doi: 10.1111/j.1365-2958.2008.06552.x19040635
22. Withers-Martinez C, Strath M, Hackett F, Haire LF, Howell SA, et al. (2014) The malaria parasite egress protease SUB1 is a calcium-dependent redox switch subtilisin. Nat Commun5: 3726. doi: 10.1038/ncomms472624785947
23. Kehr S, Sturm N, Rahlfs S, Przyborski JM, Becker K, (2010) Compartmentation of redox metabolism in malaria parasites. PLoS Pathog6: e1001242. doi: 10.1371/journal.ppat.100124221203490
24. Kowalski JM, Parekh RN, Wittrup KD, (1998) Secretion efficiency in Saccharomyces cerevisiae of bovine pancreatic trypsin inhibitor mutants lacking disulfide bonds is correlated with thermodynamic stability. Biochemistry37: 1264–1273. 9477952
25. Saridaki T, Frohlich KS, Braun-Breton C, Lanzer M, (2009) Export of PfSBP1 to the Plasmodium falciparum Maurer's clefts. Traffic10: 137–152. doi: 10.1111/j.1600-0854.2008.00860.x19054387
26. Varnai P, Balla T, (1998) Visualization of phosphoinositides that bind pleckstrin homology domains: calcium- and agonist-induced dynamic changes and relationship to myo-[3H]inositol-labeled phosphoinositide pools. J Cell Biol143: 501–510. 9786958
27. Szymczak AL, Workman CJ, Wang Y, Vignali KM, Dilioglou S, et al. (2004) Correction of multi-gene deficiency in vivo using a single 'self-cleaving' 2A peptide-based retroviral vector. Nat Biotechnol22: 589–594. 15064769
28. Straimer J, Lee MC, Lee AH, Zeitler B, Williams AE, et al. (2012) Site-specific genome editing in Plasmodium falciparum using engineered zinc-finger nucleases. Nat Methods9: 993–998. doi: 10.1038/nmeth.214322922501
29. Rug M, Cyrklaff M, Mikkonen A, Lemgruber L, Kuelzer S, et al. (2014) Export of virulence proteins by malaria-infected erythrocytes involves remodeling of host actin cytoskeleton. Blood124: 3459–3468. doi: 10.1182/blood-2014-06-58305425139348
30. Cheng Q, Cloonan N, Fischer K, Thompson J, Waine G, et al. (1998) stevor and rif are Plasmodium falciparum multicopy gene families which potentially encode variant antigens. Mol Biochem Parasitol97: 161–176. 9879895
31. Gruring C, Heiber A, Kruse F, Ungefehr J, Gilberger TW, et al. (2011) Development and host cell modifications of Plasmodium falciparum blood stages in four dimensions. Nat Commun2: 165. 21266965
32. Cooke BM, Buckingham DW, Glenister FK, Fernandez KM, Bannister LH, et al. (2006) 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 Biol172: 899–908. 16520384
33. Maier AG, Rug M, O'Neill MT, Beeson JG, Marti M, et al. (2007) Skeleton-binding protein 1 functions at the parasitophorous vacuole membrane to traffic PfEMP1 to the Plasmodium falciparum-infected erythrocyte surface. Blood109: 1289–1297. 17023587
34. Riglar DT, Rogers KL, Hanssen E, Turnbull L, Bullen HE, et al. (2013) Spatial association with PTEX complexes defines regions for effector export into Plasmodium falciparum-infected erythrocytes. Nat Commun4: 1415. doi: 10.1038/ncomms244923361006
35. Haase S, Herrmann S, Gruring C, Heiber A, Jansen PW, et al. (2009) Sequence requirements for the export of the Plasmodium falciparum Maurer's clefts protein REX2. Mol Microbiol71: 1003–1017. doi: 10.1111/j.1365-2958.2008.06582.x19170882
36. Horst M, Hilfiker-Rothenfluh S, Oppliger W, Schatz G, (1995) Dynamic interaction of the protein translocation systems in the inner and outer membranes of yeast mitochondria. EMBO J14: 2293–2297. 7774587
37. Rassow J, Guiard B, Wienhues U, Herzog V, Hartl FU, et al. (1989) Translocation arrest by reversible folding of a precursor protein imported into mitochondria. A means to quantitate translocation contact sites. J Cell Biol109: 1421–1428. 2529262
38. Sulli C, Schwartzbach SD, (1995) The polyprotein precursor to the Euglena light-harvesting chlorophyll a/b-binding protein is transported to the Golgi apparatus prior to chloroplast import and polyprotein processing. J Biol Chem270: 13084–13090. 7768903
39. Patron NJ, Waller RF, (2007) Transit peptide diversity and divergence: A global analysis of plastid targeting signals. Bioessays29: 1048–1058. 17876808
40. Grosche C, Hempel F, Bolte K, Zauner S, Maier UG, (2014) The periplastidal compartment: a naturally minimized eukaryotic cytoplasm. Curr Opin Microbiol22: 88–93. doi: 10.1016/j.mib.2014.09.01725460801
41. Zattas D, Hochstrasser M, (2015) Ubiquitin-dependent protein degradation at the yeast endoplasmic reticulum and nuclear envelope. Crit Rev Biochem Mol Biol50: 1–17. doi: 10.3109/10409238.2014.95988925231236
42. Khmelinskii A, Blaszczak E, Pantazopoulou M, Fischer B, Omnus DJ, et al. (2014) Protein quality control at the inner nuclear membrane. Nature516: 410–413. doi: 10.1038/nature1409625519137
43. Foresti O, Rodriguez-Vaello V, Funaya C, Carvalho P, (2014) Quality control of inner nuclear membrane proteins by the Asi complex. Science346: 751–755. doi: 10.1126/science.125563825236469
44. Trager W, Jensen JB, (1976) Human malaria parasites in continuous culture. Science193: 673–675. 781840
45. Spielmann T, Hawthorne PL, Dixon MW, Hannemann M, Klotz K, et al. (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. Mol Biol Cell17: 3613–3624. 16760427
46. Lambros C, Vanderberg JP, (1979) Synchronization of Plasmodium falciparum erythrocytic stages in culture. J Parasitol65: 418–420. 383936
47. Aley SB, Sherwood JA, Marsh K, Eidelman O, Howard RJ, (1986) Identification of isolate-specific proteins on sorbitol-enriched Plasmodium falciparum infected erythrocytes from Gambian patients. Parasitology92 (Pt 3): 511–525. 3526259
48. Spielmann T, Fergusen DJ, Beck HP, (2003) etramps, a new Plasmodium falciparum gene family coding for developmentally regulated and highly charged membrane proteins located at the parasite-host cell interface. Mol Biol Cell14: 1529–1544. 12686607
49. Pachlatko E, Rusch S, Muller A, Hemphill A, Tilley L, et al. (2010) MAHRP2, an exported protein of Plasmodium falciparum, is an essential component of Maurer's cleft tethers. Mol Microbiol77: 1136–1152. doi: 10.1111/j.1365-2958.2010.07278.x20624222
50. Gruring C, Spielmann T, (2012) Imaging of live malaria blood stage parasites. Methods Enzymol506: 81–92. doi: 10.1016/B978-0-12-391856-7.00029-922341220
51. Ragge K, Arnold HH, Tummler M, Knapp B, Hundt E, et al. (1990) In vitro biosynthesis and membrane translocation of the serine rich protein of Plasmodium falciparum. Mol Biochem Parasitol42: 93–100. 2122249
52. Knapp B, Hundt E, Kupper HA, (1990) Plasmodium falciparum aldolase: gene structure and localization. Mol Biochem Parasitol40: 1–12. 2190085
53. Hawthorne PL, Trenholme KR, Skinner-Adams TS, Spielmann T, Fischer K, et al. (2004) A novel Plasmodium falciparum ring stage protein, REX, is located in Maurer's clefts. Mol Biochem Parasitol136: 181–189. 15481109
54. Blisnick T, Morales Betoulle ME, Barale JC, Uzureau P, Berry L, et al. (2000) Pfsbp1, a Maurer's cleft Plasmodium falciparum protein, is associated with the erythrocyte skeleton. Mol Biochem Parasitol111: 107–121. 11087921
55. Smith AL, Friedman DB, Yu H, Carnahan RH, Reynolds AB, (2011) ReCLIP (reversible cross-link immuno-precipitation): an efficient method for interrogation of labile protein complexes. PLoS One6: e16206. doi: 10.1371/journal.pone.001620621283770
56. Distler U, Schmeisser MJ, Pelosi A, Reim D, Kuharev J, et al. (2014) In-depth protein profiling of the postsynaptic density from mouse hippocampus using data-independent acquisition proteomics. Proteomics14: 2607–2613. doi: 10.1002/pmic.20130052025211037
57. Helm D, Vissers JP, Hughes CJ, Hahne H, Ruprecht B, et al. (2014) Ion mobility tandem mass spectrometry enhances performance of bottom-up proteomics. Mol Cell Proteomics13: 3709–3715. doi: 10.1074/mcp.M114.04103825106551