The Proteome of the Isolated Containing Vacuole Reveals a Complex Trafficking Platform Enriched for Retromer Components

English version České info

The important human pathogen Chlamydia trachomatis causes 100 million new infections each year world-wide. It replicates inside the infected host cell in a unique vacuole, the inclusion. Currently, the nature, and specifically the protein composition of the inclusion, is poorly defined. Here, we described the host cell-derived inclusion proteome by quantitative proteomics using a newly established method to purify inclusions from infected epithelial cells. We showed that the inclusion is a complex intracellular trafficking platform that is well embedded into the organellar network and interacts with host cells’ antero- and retrograde trafficking pathways. Particularly, SNX1, 2, 5 and 6, components of the retromer, are recruited to the inclusion and seem to control the infection. We found also that retrograde trafficking is essential for Chlamydia progeny formation. Our study provides new insights into how the obligate intracellular bacterium C. trachomatis interacts with the eukaryotic host cell and subverts host cell functions for productive infection.

Vyšlo v časopise: The Proteome of the Isolated Containing Vacuole Reveals a Complex Trafficking Platform Enriched for Retromer Components. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004883
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004883

Souhrn

Zdroje

1. Senior K (2012) Chlamydia: a much underestimated STI. Lancet Infect Dis 12: 517–518. 22930827

2. Moulder JW (1991) Interaction of chlamydiae and host cells in vitro. Microbiol Rev 55: 143–190. 2030670

3. Heinzen RA, Hackstadt T (1997) The Chlamydia trachomatis parasitophorous vacuolar membrane is not passively permeable to low-molecular-weight compounds. Infect Immun 65: 1088–1094. 9038320

4. Saka HA, Thompson JW, Chen YS, Kumar Y, Dubois LG, et al. (2011) Quantitative proteomics reveals metabolic and pathogenic properties of Chlamydia trachomatis developmental forms. Mol Microbiol 82: 1185–1203. doi: 10.1111/j.1365-2958.2011.07877.x 22014092

5. Seaman MN (2012) The retromer complex—endosomal protein recycling and beyond. J Cell Sci 125: 4693–4702. doi: 10.1242/jcs.103440 23148298

6. Cullen PJ, Korswagen HC (2012) Sorting nexins provide diversity for retromer-dependent trafficking events. Nat Cell Biol 14: 29–37. doi: 10.1038/ncb2374 22193161

7. Worby CA, Dixon JE (2002) Sorting out the cellular functions of sorting nexins. Nat Rev Mol Cell Biol 3: 919–931. 12461558

8. Niu Y, Zhang C, Sun Z, Hong Z, Li K, et al. (2013) PtdIns(4)P regulates retromer-motor interaction to facilitate dynein-cargo dissociation at the trans-Golgi network. Nat Cell Biol 15: 417–429. doi: 10.1038/ncb2710 23524952

9. Hong Z, Yang Y, Zhang C, Niu Y, Li K, et al. (2009) The retromer component SNX6 interacts with dynactin p150(Glued) and mediates endosome-to-TGN transport. Cell Res 19: 1334–1349. doi: 10.1038/cr.2009.130 19935774

10. Garin J, Diez R, Kieffer S, Dermine JF, Duclos S, et al. (2001) The phagosome proteome: insight into phagosome functions. J Cell Biol 152: 165–180. 11149929

11. Gotthardt D, Warnatz HJ, Henschel O, Bruckert F, Schleicher M, et al. (2002) High-resolution dissection of phagosome maturation reveals distinct membrane trafficking phases. Mol Biol Cell 13: 3508–3520. 12388753

12. Gotthardt D, Blancheteau V, Bosserhoff A, Ruppert T, Delorenzi M, et al. (2006) Proteomics fingerprinting of phagosome maturation and evidence for the role of a Galpha during uptake. Mol Cell Proteomics 5: 2228–2243. 16926386

13. Sturgill-Koszycki S, Haddix PL, Russell DG (1997) The interaction between Mycobacterium and the macrophage analyzed by two-dimensional polyacrylamide gel electrophoresis. Electrophoresis 18: 2558–2565. 9527485

14. Mills SD, Finlay BB (1998) Isolation and characterization of Salmonella typhimurium and Yersinia pseudotuberculosis-containing phagosomes from infected mouse macrophages: Y. pseudotuberculosis traffics to terminal lysosomes where they are degraded. Eur J Cell Biol 77: 35–47. 9808287

15. Luhrmann A, Haas A (2000) A method to purify bacteria-containing phagosomes from infected macrophages. Methods Cell Sci 22: 329–341. 11549946

16. Urwyler S, Nyfeler Y, Ragaz C, Lee H, Mueller LN, et al. (2009) Proteome analysis of Legionella vacuoles purified by magnetic immunoseparation reveals secretory and endosomal GTPases. Traffic 10: 76–87. doi: 10.1111/j.1600-0854.2008.00851.x 18980612

17. Shevchuk O, Batzilla C, Hagele S, Kusch H, Engelmann S, et al. (2009) Proteomic analysis of Legionella-containing phagosomes isolated from Dictyostelium. Int J Med Microbiol 299: 489–508. doi: 10.1016/j.ijmm.2009.03.006 19482547

18. Rockey DD, Heinzen RA, Hackstadt T (1995) Cloning and characterization of a Chlamydia psittaci gene coding for a protein localized in the inclusion membrane of infected cells. Mol Microbiol 15: 617–626. 7783634

19. Rzomp KA, Scholtes LD, Briggs BJ, Whittaker GR, Scidmore MA (2003) Rab GTPases are recruited to chlamydial inclusions in both a species-dependent and species-independent manner. Infect Immun 71: 5855–5870. 14500507

20. Ong SE, Blagoev B, Kratchmarova I, Kristensen DB, Steen H, et al. (2002) Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 1: 376–386. 12118079

21. Schwanhausser B, Busse D, Li N, Dittmar G, Schuchhardt J, et al. (2011) Global quantification of mammalian gene expression control. Nature 473: 337–342. doi: 10.1038/nature10098 21593866

22. Nagaraj N, Wisniewski JR, Geiger T, Cox J, Kircher M, et al. (2011) Deep proteome and transcriptome mapping of a human cancer cell line. Mol Syst Biol 7: 548. doi: 10.1038/msb.2011.81 22068331

23. UniProt C (2014) Activities at the Universal Protein Resource (UniProt). Nucleic Acids Res 42: D191–198. doi: 10.1093/nar/gkt1140 24253303

24. Capmany A, Damiani MT (2010) Chlamydia trachomatis intercepts Golgi-derived sphingolipids through a Rab14-mediated transport required for bacterial development and replication. PLoS One 5: e14084. doi: 10.1371/journal.pone.0014084 21124879

25. Derre I, Swiss R, Agaisse H (2011) The lipid transfer protein CERT interacts with the Chlamydia inclusion protein IncD and participates to ER-Chlamydia inclusion membrane contact sites. PLoS Pathog 7: e1002092. doi: 10.1371/journal.ppat.1002092 21731489

26. Elwell CA, Jiang S, Kim JH, Lee A, Wittmann T, et al. (2011) Chlamydia trachomatis co-opts GBF1 and CERT to acquire host sphingomyelin for distinct roles during intracellular development. PLoS Pathog 7: e1002198. doi: 10.1371/journal.ppat.1002198 21909260

27. Scidmore MA, Hackstadt T (2001) Mammalian 14-3-3beta associates with the Chlamydia trachomatis inclusion membrane via its interaction with IncG. Mol Microbiol 39: 1638–1650. 11260479

28. Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, et al. (2013) STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res 41: D808–815. doi: 10.1093/nar/gks1094 23203871

29. Stechmann B, Bai SK, Gobbo E, Lopez R, Merer G, et al. (2010) Inhibition of retrograde transport protects mice from lethal ricin challenge. Cell 141: 231–242. doi: 10.1016/j.cell.2010.01.043 20403321

30. Hoffmann C, Finsel I, Otto A, Pfaffinger G, Rothmeier E, et al. (2013) Functional analysis of novel Rab GTPases identified in the proteome of purified Legionella-containing vacuoles from macrophages. Cell Microbiol.

31. Chiappino ML, Dawson C, Schachter J, Nichols BA (1995) Cytochemical localization of glycogen in Chlamydia trachomatis inclusions. J Bacteriol 177: 5358–5363. 7545158

32. Cocchiaro JL, Kumar Y, Fischer ER, Hackstadt T, Valdivia RH (2008) Cytoplasmic lipid droplets are translocated into the lumen of the Chlamydia trachomatis parasitophorous vacuole. Proc Natl Acad Sci U S A 105: 9379–9384. doi: 10.1073/pnas.0712241105 18591669

33. Campbell-Valois FX, Trost M, Chemali M, Dill BD, Laplante A, et al. (2012) Quantitative proteomics reveals that only a subset of the endoplasmic reticulum contributes to the phagosome. Mol Cell Proteomics 11: M111 016378.

34. Fields KA, Hackstadt T (2002) The chlamydial inclusion: escape from the endocytic pathway. Annu Rev Cell Dev Biol 18: 221–245. 12142274

35. Stephens RS, Kalman S, Lammel C, Fan J, Marathe R, et al. (1998) Genome sequence of an obligate intracellular pathogen of humans: Chlamydia trachomatis. Science 282: 754–759. 9784136

36. Nelson CD, Carney DW, Derdowski A, Lipovsky A, Gee GV, et al. (2013) A retrograde trafficking inhibitor of ricin and Shiga-like toxins inhibits infection of cells by human and monkey polyomaviruses. MBio 4: e00729–00713. doi: 10.1128/mBio.00729-13 24222489

37. Lipovsky A, Popa A, Pimienta G, Wyler M, Bhan A, et al. (2013) Genome-wide siRNA screen identifies the retromer as a cellular entry factor for human papillomavirus. Proc Natl Acad Sci U S A 110: 7452–7457. doi: 10.1073/pnas.1302164110 23569269

38. Sandvig K, Garred O, Prydz K, Kozlov JV, Hansen SH, et al. (1992) Retrograde transport of endocytosed Shiga toxin to the endoplasmic reticulum. Nature 358: 510–512. 1641040

39. Bujny MV, Ewels PA, Humphrey S, Attar N, Jepson MA, et al. (2008) Sorting nexin-1 defines an early phase of Salmonella-containing vacuole-remodeling during Salmonella infection. J Cell Sci 121: 2027–2036. doi: 10.1242/jcs.018432 18505799

40. Braun V, Wong A, Landekic M, Hong WJ, Grinstein S, et al. (2010) Sorting nexin 3 (SNX3) is a component of a tubular endosomal network induced by Salmonella and involved in maturation of the Salmonella-containing vacuole. Cell Microbiol 12: 1352–1367. doi: 10.1111/j.1462-5822.2010.01476.x 20482551

41. Peter BJ, Kent HM, Mills IG, Vallis Y, Butler PJ, et al. (2004) BAR domains as sensors of membrane curvature: the amphiphysin BAR structure. Science 303: 495–499. 14645856

42. Carlton J, Bujny M, Peter BJ, Oorschot VM, Rutherford A, et al. (2004) Sorting nexin-1 mediates tubular endosome-to-TGN transport through coincidence sensing of high- curvature membranes and 3-phosphoinositides. Curr Biol 14: 1791–1800. 15498486

43. Moorhead AM, Jung JY, Smirnov A, Kaufer S, Scidmore MA (2010) Multiple host proteins that function in phosphatidylinositol-4-phosphate metabolism are recruited to the chlamydial inclusion. Infect Immun 78: 1990–2007. doi: 10.1128/IAI.01340-09 20231409

44. Swarbrick JD, Shaw DJ, Chhabra S, Ghai R, Valkov E, et al. (2011) VPS29 is not an active metallo-phosphatase but is a rigid scaffold required for retromer interaction with accessory proteins. PLoS One 6: e20420. doi: 10.1371/journal.pone.0020420 21629666

45. Nisar S, Kelly E, Cullen PJ, Mundell SJ (2010) Regulation of P2Y1 receptor traffic by sorting Nexin 1 is retromer independent. Traffic 11: 508–519. doi: 10.1111/j.1600-0854.2010.01035.x 20070609

46. Prosser DC, Tran D, Schooley A, Wendland B, Ngsee JK (2010) A novel, retromer-independent role for sorting nexins 1 and 2 in RhoG-dependent membrane remodeling. Traffic 11: 1347–1362. doi: 10.1111/j.1600-0854.2010.01100.x 20604901

47. Chua CE, Lim YS, Lee MG, Tang BL (2012) Non-classical membrane trafficking processes galore. J Cell Physiol 227: 3722–3730. doi: 10.1002/jcp.24082 22378347

48. Tan X, Sun Y, Thapa N, Liao Y, Hedman AC, et al. (2015) LAPTM4B is a PtdIns(4,5)P2 effector that regulates EGFR signaling, lysosomal sorting, and degradation. EMBO J 34: 475–490. doi: 10.15252/embj.201489425 25588945

49. Seaman MN (2004) Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer. J Cell Biol 165: 111–122. 15078902

50. Patel AL, Chen X, Wood ST, Stuart ES, Arcaro KF, et al. (2014) Activation of epidermal growth factor receptor is required for Chlamydia trachomatis development. BMC Microbiol 14: 277. doi: 10.1186/s12866-014-0277-4 25471819

51. Zhou B, Yun EY, Ray L, You J, Ip YT, et al. (2014) Retromer promotes immune quiescence by suppressing Spatzle-Toll pathway in Drosophila. J Cell Physiol 229: 512–520. doi: 10.1002/jcp.24472 24343480

52. Johannes L, Popoff V (2008) Tracing the retrograde route in protein trafficking. Cell 135: 1175–1187. doi: 10.1016/j.cell.2008.12.009 19109890

53. Moore ER, Mead DJ, Dooley CA, Sager J, Hackstadt T (2011) The trans-Golgi SNARE syntaxin 6 is recruited to the chlamydial inclusion membrane. Microbiology 157: 830–838. doi: 10.1099/mic.0.045856-0 21109560

54. Kabeiseman EJ, Cichos K, Hackstadt T, Lucas A, Moore ER (2013) Vesicle-associated membrane protein 4 and syntaxin 6 interactions at the chlamydial inclusion. Infect Immun 81: 3326–3337. doi: 10.1128/IAI.00584-13 23798538

55. Banhart S, Saied EM, Martini A, Koch S, Aeberhard L, et al. (2014) Improved plaque assay identifies a novel anti-Chlamydia ceramide derivative with altered intracellular localization. Antimicrob Agents Chemother.

56. Cox J, Mann M (2008) MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification. Nat Biotechnol 26: 1367–1372. doi: 10.1038/nbt.1511 19029910

57. Eden E, Navon R, Steinfeld I, Lipson D, Yakhini Z (2009) GOrilla: a tool for discovery and visualization of enriched GO terms in ranked gene lists. BMC Bioinformatics 10: 48. doi: 10.1186/1471-2105-10-48 19192299