The aspartyl protease TgASP5 mediates the export of the Toxoplasma GRA16 and GRA24 effectors into host cells

Cellular Microbiology

Volumn 18, Issue 2, 2016, Pages 151-167

  Curt Varesano, Aurélie ^a,b   Braun, Laurence ^a,b   Ranquet, Caroline ^c   Hakimi, Mohamed Ali ^a,b   Bougdour, Alexandre ^a,b  

^a CNRS   (France)

^b UNIV GRENOBLE ALPES   (France)

^c BGene Genetics SAS   (France)

Author keywords

Apicomplexa; Microbial cell interaction; Protein export; Protein trafficking

Indexed keywords

ASPARTIC PROTEINASE; EPITOPE; PROTOZOAL PROTEIN;

AMINO TERMINAL SEQUENCE; ARTICLE; HOST CELL; NONHUMAN; PLASMODIUM; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN MOTIF; PROTEIN PROCESSING; TOXOPLASMA; TOXOPLASMA GONDII; CELL CULTURE; ENZYMOLOGY; FIBROBLAST; HUMAN; METABOLISM; PARASITOLOGY; PROTEIN TRANSPORT;

ASPARTIC ACID PROTEASES; CELLS, CULTURED; FIBROBLASTS; HUMANS; PROTEIN PROCESSING, POST-TRANSLATIONAL; PROTEIN TRANSPORT; PROTOZOAN PROTEINS; TOXOPLASMA;

EID: 84955105079     PISSN: 14625814     EISSN: 14625822     Source Type: Journal    
DOI: 10.1111/cmi.12498     Document Type: Article

References (32)

1. Beck, J.R., Muralidharan, V., Oksman, A. and Goldberg, D.E. (2014) PTEX component HSP101 mediates export of diverse malaria effectors into host erythrocytes. Nature 511: 592-595.
2. 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: 2418-2426.
3. Boddey, J.A., Carvalho, T.G., Hodder, A.N., Sargeant, T.J., Sleebs, B.E., Marapana, D., et al. (2013a) Role of plasmepsin V in export of diverse protein families from the Plasmodium falciparum exportome. Traffic 14: 532-550.
4. Boddey, J.A. and Cowman, A.F. (2013b) Plasmodium nesting: remaking the erythrocyte from the inside out. Annu Rev Microbiol 67: 243-269.
5. Boddey, J.A., Hodder, A.N., Gunther, S., Gilson, P.R., Patsiouras, H., Kapp, E.A., et al. (2010) An aspartyl protease directs malaria effector proteins to the host cell. Nature 463: 627-631.
6. Bougdour, A., Durandau, E., Brenier-Pinchart, M.P., Ortet, P., Barakat, M., Kieffer, S., et al. (2013) Host cell subversion by Toxoplasma GRA16, an exported dense granule protein that targets the host cell nucleus and alters gene expression. Cell Host Microbe 13: 489-500.
7. Bougdour, A., Maubon, D., Baldacci, P., Ortet, P., Bastien, O., Bouillon, A., et al. (2009) Drug inhibition of HDAC3 and epigenetic control of differentiation in Apicomplexa parasites. J Exp Med 206: 953-966.
8. Bougdour, A., Tardieux, I. and Hakimi, M.A. (2014) Toxoplasma exports dense granule proteins beyond the vacuole to the host cell nucleus and rewires the host genome expression. Cell Microbiol 16: 334-343.
9. Bougdour, A., Wickner, S. and Gottesman, S. (2006) Modulating RssB activity: IraP, a novel regulator of sigma(S) stability in Escherichia coli. Genes Dev 20: 884-897.
10. Braun, L., Brenier-Pinchart, M.P., Yogavel, M., Curt-Varesano, A., Curt-Bertini, R.L., Hussain, T., et al. (2013) A Toxoplasma dense granule protein, GRA24, modulates the early immune response to infection by promoting a direct and sustained host p38 MAPK activation. J Exp Med 210: 2071-2086.
11. Cong, L., Ran, F.A., Cox, D., Lin, S., Barretto, R., Habib, N., et al. (2013) Multiplex genome engineering using CRISPR/Cas systems. Science 339: 819-823.
12. Donald, R.G. and Roos, D.S. (1993) Stable molecular transformation of Toxoplasma gondii: a selectable dihydrofolate reductase-thymidylate synthase marker based on drug-resistance mutations in malaria. Proc Natl Acad Sci U S A 90: 11703-11707.
13. Elsworth, B., Matthews, K., Nie, C.Q., Kalanon, M., Charnaud, S.C., Sanders, P.R., et al. (2014) PTEX is an essential nexus for protein export in malaria parasites. Nature 511: 587-591.
14. 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. Mol Microbiol 71: 613-628.
15. Gold, Daniel A., Kaplan, Aaron D., Lis, A., Bett, Glenna C.L., Rosowski, Emily E., Cirelli, Kimberly M., 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 Microbe 17: 642-652.
16. Gruring, C., Heiber, A., Kruse, F., Flemming, S., Franci, G., Colombo, S.F., et al. (2012) Uncovering common principles in protein export of malaria parasites. Cell Host Microbe 12: 717-729.
17. Haase, S. and de Koning-Ward, T.F. (2010) New insights into protein export in malaria parasites. Cell Microbiol 12: 580-587.
18. Haase, S., Herrmann, S., Gruring, C., Heiber, A., Jansen, P.W., Langer, C., et al. (2009) Sequence requirements for the export of the Plasmodium falciparum Maurer's clefts protein REX2. Mol Microbiol 71: 1003-1017.
19. Hakimi, M.A. and Bougdour, A. (2015) Toxoplasma's ways of manipulating the host transcriptome via secreted effectors. Curr Opin Microbiol 26: 24-31.
20. Heiber, A., Kruse, F., Pick, C., Gruring, C., Flemming, S., Oberli, A., et al. (2013) Identification of new PNEPs indicates a substantial non-PEXEL exportome and underpins common features in Plasmodium falciparum protein export. PLoS Pathog 9: e1003546.
21. 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: 1934-1937.
22. Hsiao, C.H., Luisa Hiller, N., Haldar, K. and Knoll, L.J. (2013) A HT/PEXEL motif in Toxoplasma dense granule proteins is a signal for protein cleavage but not export into the host cell. Traffic 14: 519-531.
23. Huynh, M.H. and Carruthers, V.B. (2009) Tagging of endogenous genes in a Toxoplasma gondii strain lacking Ku80. Eukaryot Cell 8: 530-539.
24. 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: 632-636.
25. Shea, M., Jakle, U., Liu, Q., Berry, C., Joiner, K.A. and Soldati-Favre, D. (2007) A family of aspartic proteases and a novel, dynamic and cell-cycle-dependent protease localization in the secretory pathway of Toxoplasma gondii. Traffic 8: 1018-1034.
26. Shen, B., Brown, K.M., Lee, T.D. and Sibley, L.D. (2014) Efficient gene disruption in diverse strains of Toxoplasma gondii using CRISPR/CAS9. MBio 5: e01114-01114.
27. Sidik, S.M., Hackett, C.G., Tran, F., Westwood, N.J. and Lourido, S. (2014) Efficient genome engineering of Toxoplasma gondii using CRISPR/Cas9. PLoS One 9: e100450.
28. Sleebs, B.E., Lopaticki, S., Marapana, D.S., O'Neill, M.T., Rajasekaran, P., Gazdik, M., et al. (2014) Inhibition of plasmepsin V activity demonstrates its essential role in protein export, PfEMP1 display, and survival of malaria parasites. PLoS Biol 12: e1001897.
29. Spillman, N.J., Beck, J.R. and Goldberg, D.E. (2015) Protein export into malaria parasite-infected erythrocytes: mechanisms and functional consequences. Annu Rev Biochem.
30. van Rooyen, J.M., Hakimi, M.A. and Belrhali, H. (2015) Recombinant expression, purification, and crystallization of the glutaminyl-tRNA synthetase from Toxoplasma gondii. Protein Expr Purif 110: 115-121.
31. Weber, E., Gruetzner, R., Werner, S., Engler, C. and Marillonnet, S. (2011) Assembly of designer TAL effectors by Golden Gate cloning. PLoS One 6: e19722.
32. Zhou, Y., Zhu, S., Cai, C., Yuan, P., Li, C., Huang, Y. and Wei, W. (2014) High-throughput screening of a CRISPR/Cas9 library for functional genomics in human cells. Nature 509: 487-491.