Beyond rab gtpases legionella activates the small gtpase ran to promote microtubule polymerization, pathogen vacuole motility, and infection

Small GTPases

Volumn 5, Issue 3, 2014, Pages

  Hilbi, Hubert ^a,b   Rothmeier, Eva ^a   Hoffmann, Christine ^a   Harrison, Christopher F ^a  

^a UNIVERSITY OF MUNICH   (Germany)

^b UNIVERSITY OF ZURICH   (Switzerland)

Author keywords

Acanthamoeba; Bacterial effector protein; Dictyostelium; Guanine nucleotide exchange factor; Host pathogen interactions; Legionella; Macrophage; Microtubules; Pathogen vacuole; Small GTPase; Type IV secretion

Indexed keywords

BACTERIAL PROTEIN; PROTEIN LEGG1; RAB PROTEIN; RAN PROTEIN; UNCLASSIFIED DRUG;

ARTICLE; BACTERIAL INFECTION; CELL MIGRATION; CELL MOTILITY; CELL VACUOLE; ENDOSOME; ENZYME ACTIVATION; HOST PATHOGEN INTERACTION; HUMAN; LEGIONELLA; LEGIONELLA PNEUMOPHILA; MICROTUBULE ASSEMBLY; NONHUMAN; PHAGOCYTE; PROTEIN LOCALIZATION; AMOEBA (LIFE CYCLE STAGE); ENZYMOLOGY; MACROPHAGE; METABOLISM; MICROBIOLOGY; MICROTUBULE; PATHOGENICITY; PHYSIOLOGY;

ACANTHAMOEBA; BACTERIA (MICROORGANISMS); DICTYOSTELIUM; LEGIONELLA; LEGIONELLA PNEUMOPHILA; PROTOZOA;

AMOEBA; BACTERIAL PROTEINS; HOST-PATHOGEN INTERACTIONS; LEGIONELLA PNEUMOPHILA; MACROPHAGES; MICROTUBULES; RAN GTP-BINDING PROTEIN; VACUOLES;

EID: 84917693090     PISSN: 21541248     EISSN: 21541256     Source Type: Journal    
DOI: 10.4161/21541248.2014.972859     Document Type: Article

References (71)

1. Hilbi H, Hoffmann C, Harrison CF. Legionella spp. outdoors: colonization, communication and persistence. Environ Microbiol Rep 2011; 3:286-96; PMID:23761274; http://dx.doi.org/10.1111/j.1758-2229.2011.00247.x
2. Newton HJ, Ang DK, van Driel IR, Hartland EL. Molecular pathogenesis of infections caused by Legionella pneumophila. Clin Microbiol Rev 2010; 23:274-98; PMID:20375353; http://dx.doi.org/10.1128/CMR.00052-09
3. Nguyen TM, Ilef D, Jarraud S, Rouil L, Campese C, Che D, Haeghebaert S, Ganiayre F, Marcel F, Etienne J, et al. A community-wide outbreak of legionnaires disease linked to industrial cooling towers–how far can contaminated aerosols spread? J Infect Dis 2006; 193:102-11; PMID:16323138; http://dx.doi.org/10.1086/498575
4. Isberg RR, O’Connor TJ, Heidtman M. The Legionella pneumophila replication vacuole: making a cosy niche inside host cells. Nat Rev Microbiol 2009; 7:13-24; PMID:19011659; http://dx.doi.org/10.1038/nrmicro1967
5. Hubber A, Roy CR. Modulation of host cell function by Legionella pneumophila type IV effectors. Annu Rev Cell Dev Biol 2010; 26:261-83; PMID:20929312; http://dx.doi.org/10.1146/annurev-cellbio-100109-104034
6. Hilbi H, Haas A. Secretive bacterial pathogens and the secretory pathway. Traffic 2012; 13:1187-97; PMID:22340894; http://dx.doi.org/10.1111/j.1600-0854.2012.01344.x
7. Ragaz C, Pietsch H, Urwyler S, Tiaden A, Weber SS, Hilbi H. The Legionella pneumophila phosphatidylinositol-4 phosphate-binding type IV substrate SidC recruits endoplasmic reticulum vesicles to a replicationpermissive vacuole. Cell Microbiol 2008; 10:2416-33; PMID:18673369; http://dx.doi.org/10.1111/j.1462-5822.2008.01219.x
8. Weber S, Wagner M, Hilbi H. Live-cell imaging of phosphoinositide dynamics and membrane architecture during Legionella infection. MBio 2013; 5:e00839-13; PMID:24473127
9. Finsel I, Ragaz C, Hoffmann C, Harrison CF, Weber S, van Rahden VA, Johannes L, Hilbi H. The Legionella effector RidL inhibits retrograde trafficking to promote intracellular replication. Cell Host Microbe 2013; 14:38–50; PMID:23870312; http://dx.doi.org/10.1016/j.chom.2013.06.001
10. Xu L, Shen X, Bryan A, Banga S, Swanson MS, Luo ZQ. Inhibition of host vacuolar H C-ATPase activity by a Legionella pneumophila effector. PLoS Pathog 2010; 6:e1000822; PMID:20333253; http://dx.doi.org/10.1371/journal.ppat.1000822
11. Choy A, Dancourt J, Mugo B, O’Connor TJ, Isberg RR, Melia TJ, Roy CR. The Legionella effector RavZ inhibits host autophagy through irreversible Atg8 deconjugation. Science 2012; 338:1072-6; PMID:23112293; http://dx.doi.org/10.1126/science.1227026
12. Hoffmann C, Harrison CF, Hilbi H. The natural alternative: protozoa as cellular models for Legionella infection. Cell Microbiol 2014; 16:15-26; PMID:24168696; http://dx.doi.org/10.1111/cmi.12235
13. Zhu W, Banga S, Tan Y, Zheng C, Stephenson R, Gately J, Luo ZQ. Comprehensive identification of protein substrates of the Dot/Icm type IV transporter of Legionella pneumophila. PLoS One 2011; 6:e17638; PMID:21408005; http://dx.doi.org/10.1371/journal.pone.0017638
14. Gomez-Valero L, Rusniok C, Cazalet C, Buchrieser C. Comparative and functional genomics of Legionella identified eukaryotic like proteins as key players in host-pathogen interactions. Front Microbiol 2011; 2:208; PMID:22059087; http://dx.doi.org/10.3389/fmicb.2011.00208
15. Lifshitz Z, Burstein D, Peeri M, Zusman T, Schwartz K, Shuman HA, Pupko T, Segal G. Computational modeling and experimental validation of the Legionella and Coxiella virulence-related type-IVB secretion signal. Proc Natl Acad Sci U S A 2013; 110:E707-15; PMID:23382224; http://dx.doi.org/10.1073/pnas.1215278110
16. Haneburger I, Hilbi H. Phosphoinositide lipids and the Legionella pathogen vacuole. Curr Top Microbiol Immunol 2013; 376:155-73; PMID:23918172; http://dx.doi.org/10.1007/82_2013_341
17. Hilbi H, Weber S, Finsel I. Anchors for effectors: subversion of phosphoinositide lipids by Legionella. Front Microbiol 2011; 2:91; PMID:21833330; http://dx.doi.org/10.3389/fmicb.2011.00091
18. Weber SS, Ragaz C, Hilbi H. Pathogen trafficking pathways and host phosphoinositide metabolism. Mol Microbiol 2009; 71:1341-52; PMID:19208094; http://dx.doi.org/10.1111/j.1365-2958.2009.06608.x
19. Weber S, Dolinsky S, Hilbi H. Interactions of Legionella effector proteins with host phosphoinositide lipids. Methods Mol Biol 2013; 954:367-80; PMID:23150409; http://dx.doi.org/10.1007/978-1-62703-161-5_23
20. Weber SS, Ragaz C, Reus K, Nyfeler Y, Hilbi H. Legionella pneumophila exploits PI(4)P to anchor secreted effector proteins to the replicative vacuole. PLoS Pathog 2006; 2:e46; PMID:16710455; http://dx.doi.org/10.1371/journal.ppat.0020046
21. Brombacher E, Urwyler S, Ragaz C, Weber SS, Kami K, Overduin M, HilbiH. Rab1 guanine nucleotide exchange factor SidM is a major phosphatidylinositol 4-phosphatebinding effector protein of Legionella pneumophila. J Biol Chem 2009; 284:4846-56; PMID:19095644; http://dx.doi.org/10.1074/jbc.M807505200
22. Schoebel S, Blankenfeldt W, Goody RS, Itzen A. Highaffinity binding of phosphatidylinositol 4-phosphate by Legionella pneumophila DrrA. EMBO Rep 2010; 11:598-604; PMID:20616805; http://dx.doi.org/10.1038/embor.2010.97
23. Hsu F, Zhu W, Brennan L, Tao L, Luo ZQ, Mao Y. Structural basis for substrate recognition by a unique Legionella phosphoinositide phosphatase. Proc Natl Acad Sci U S A 2012; 109:13567-72; PMID:22872863; http://dx.doi.org/10.1073/pnas.1207903109
24. Weber SS, Ragaz C, Hilbi H. The inositol polyphosphate 5-phosphatase OCRL1 restricts intracellular growth of Legionella, localizes to the replicative vacuole and binds to the bacterial effector LpnE. Cell Microbiol 2009; 11:442-60; PMID:19021631; http://dx.doi.org/10.1111/j.1462-5822.2008.01266.x
25. Jank T, B€ohmer KE, Tzivelekidis T, Schwan C, Belyi Y, Aktories K. Domain organization of Legionella effector SetA. Cell Microbiol 2012; 14:852-68; PMID:22288428; http://dx.doi.org/10.1111/j.1462-5822.2012.01761.x
26. Toulabi L, Wu X, Cheng Y, Mao Y. Identification and structural characterization of a Legionella phosphoinositide phosphatase. J Biol Chem 2013; 288:24518-27; PMID:23843460; http://dx.doi.org/10.1074/jbc.M113.474239
27. Itzen A, Goody RS. Covalent coercion by Legionella pneumophila. Cell Host Microbe 2011; 10:89-91; PMID:21843863; http://dx.doi.org/10.1016/j.chom.2011.08.002
28. Sherwood RK, Roy CR. A Rab-centric perspective of bacterial pathogen-occupied vacuoles. Cell Host Microbe 2013; 14:256-68; PMID:24034612; http://dx.doi.org/10.1016/j.chom.2013.08.010
29. Nagai H, Kagan JC, Zhu X, Kahn RA, Roy CR. A bacterial guanine nucleotide exchange factor activates ARF on Legionella phagosomes. Science 2002; 295:679-82; PMID:11809974; http://dx.doi.org/10.1126/science.1067025
30. Murata T, Delprato A, Ingmundson A, Toomre DK, Lambright DG, Roy CR. The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotideexchange factor. Nat Cell Biol 2006; 8:971-7; PMID:16906144; http://dx.doi.org/10.1038/ncb1463
31. Machner MP, Isberg RR. Targeting of host Rab GTPase function by the intravacuolar pathogen Legionella pneumophila. Dev Cell 2006; 11:47–56; PMID:16824952; http://dx.doi.org/10.1016/j.devcel.2006.05.013
32. Muller MP, Peters H, Blumer J, Blankenfeldt W, Goody RS, Itzen A. The Legionella effector protein DrrA AMPylates the membrane traffic regulator Rab1b. Science 2010; 329:946-9; PMID:20651120; http://dx.doi.org/10.1126/science.1192276
33. Mukherjee S, Liu X, Arasaki K, McDonough J, Galán JE, Roy CR. Modulation of Rab GTPase function by a protein phosphocholine transferase. Nature 2011; 477:103-6; PMID:21822290; http://dx.doi.org/10.1038/nature10335
34. Pan X, Luhrmann A, Satoh A, Laskowski-Arce MA, Roy CR. Ankyrin repeat proteins comprise a diverse family of bacterial type IV effectors. Science 2008; 320:1651-4; PMID:18566289; http://dx.doi.org/10.1126/science.1158160
35. Schoebel S, Cichy AL, Goody RS, Itzen A. Protein LidA from Legionella is a Rab GTPase supereffector. Proc Natl Acad Sci U S A 2011; 108:17945–50; PMID:22011575; http://dx.doi.org/10.1073/pnas.1113133108
36. Tan Y, Luo ZQ. Legionella pneumophila SidD is a deAMPylase that modifies Rab1. Nature 2011; 475:506-9; PMID:21734656; http://dx.doi.org/10.1038/nature10307
37. Neunuebel MR, Chen Y, Gaspar AH, Backlund PS Jr., Yergey A, Machner MP. De-AMPylation of the small GTPase Rab1 by the pathogen Legionella pneumophila. Science 2011; 333:453-6; PMID:21680813; http://dx.doi.org/10.1126/science.1207193
38. Tan Y, Arnold RJ, Luo ZQ. Legionella pneumophila regulates the small GTPase Rab1 activity by reversible phosphorylcholination. Proc Natl Acad Sci U S A 2011; 108:21212-7; PMID:22158903; http://dx.doi.org/10.1073/pnas.1114023109
39. Goody PR, Heller K, Oesterlin LK, Muller MP, Itzen A, Goody RS. Reversible phosphocholination of Rab proteins by Legionella pneumophila effector proteins. EMBO J 2012; 31:1774-84; PMID:22307087; http://dx.doi.org/10.1038/emboj.2012.16
40. Ingmundson A, Delprato A, Lambright DG, Roy CR. Legionella pneumophila proteins that regulate Rab1 membrane cycling. Nature 2007; 450:365-9; PMID:17952054; http://dx.doi.org/10.1038/nature06336
41. Gazdag ME, Streller A, Haneburger I, Hilbi H, Vetter IR, Goody RS, Itzen A. Mechanism of Rab1b deactivation by the Legionella pneumophila GAP LepB. EMBO Rep 2013; 14:199-205; PMID:23288104; http://dx.doi.org/10.1038/embor.2012.211
42. Ku B, Lee KH, Park WS, Yang CS, Ge J, Lee SG, Cha SS, Shao F, Heo WD, Jung JU, et al. VipD of Legionella pneumophila targets activated Rab5 and Rab22 to interfere with endosomal trafficking in macrophages. PLoS Pathog 2012; 8:e1003082; PMID:23271971; http://dx.doi.org/10.1371/journal.ppat.1003082
43. Gaspar AH, Machner MP. VipD is a Rab5-activated phospholipase A1 that protects Legionella pneumophila from endosomal fusion. Proc Natl Acad Sci U S A 2014; 111:4560-4565; PMID:24616501; http://dx.doi.org/10.1073/pnas.1316376111
44. Degtyar E, Zusman T, Ehrlich M, Segal G. A Legionella effector acquired from protozoa is involved in sphingolipids metabolism and is targeted to the host cell mitochondria. Cell Microbiol 2009; 11:1219-35; PMID:19438520; http://dx.doi.org/10.1111/j.1462-5822.2009.01328.x
45. Kagan JC, Roy CR. Legionella phagosomes intercept vesicular traffic from endoplasmic reticulum exit sites. Nat Cell Biol 2002; 4:945-54; PMID:12447391; http://dx.doi.org/10.1038/ncb883
46. Kagan JC, Stein MP, Pypaert M, Roy CR. Legionella subvert the functions of Rab1 and Sec22b to create a replicative organelle. J Exp Med 2004; 199:1201-11; PMID:15117975; http://dx.doi.org/10.1084/jem.20031706
47. Derré I, Isberg RR. Legionella pneumophila replication vacuole formation involves rapid recruitment of proteins of the early secretory system. Infect Immun 2004; 72:3048-53; PMID:15102819; http://dx.doi.org/10.1128/IAI.72.5.3048-3053.2004
48. Clemens DL, Lee BY, Horwitz MA. Mycobacterium tuberculosis and Legionella pneumophila phagosomes exhibit arrested maturation despite acquisition of Rab7. Infect Immun 2000; 68:5154-66; PMID:10948139; http://dx.doi.org/10.1128/IAI.68.9.5154-5166.2000
49. Urwyler S, Nyfeler Y, Ragaz C, Lee H, Mueller LN, Aebersold R, Hilbi H. Proteome analysis of Legionella vacuoles purified by magnetic immunoseparation reveals secretory and endosomal GTPases. Traffic 2009; 10:76-87; PMID:18980612; http://dx.doi.org/10.1111/j.1600-0854.2008.00851.x
50. Shevchuk O, Batzilla C, Hagele S, Kusch H, Engelmann S, Hecker M, Haas A, Heuner K, Glockner G, Steinert M. Proteomic analysis of Legionella-containing phagosomes isolated from Dictyostelium. Int J Med Microbiol 2009; 299:489-508; PMID:19482547; http://dx.doi.org/10.1016/j.ijmm.2009.03.006
51. Hoffmann C, Finsel I, Otto A, Pfaffinger G, Rothmeier E, Hecker M, Becher D, Hilbi H. Functional analysis of novel Rab GTPases identified in the proteome of purified Legionella-containing vacuoles from macrophages. Cell Microbiol 2014; 16:1034-52; PMID:24373249
52. Lu H, Clarke M. Dynamic properties of Legionellacontaining phagosomes in Dictyostelium amoebae. Cell Microbiol 2005; 7:995-1007; PMID:15953031; http://dx.doi.org/10.1111/j.1462-5822.2005.00528.x
53. Stewart M. Molecular mechanism of the nuclear protein import cycle. Nat Rev Mol Cell Biol 2007; 8:195-208; PMID:17287812; http://dx.doi.org/10.1038/nrm2114
54. Goodman B, Zheng Y. Mitotic spindle morphogenesis: Ran on the microtubule cytoskeleton and beyond. Biochem Soc Trans 2006; 34:716-21; PMID:17052181; http://dx.doi.org/10.1042/BST0340716
55. Clarke PR, Zhang C. Spatial and temporal coordination of mitosis by Ran GTPase. Nat Rev Mol Cell Biol 2008; 9:464-77; PMID:18478030; http://dx.doi.org/10.1038/nrm2410
56. Joseph J. Ran at a glance. J Cell Sci 2006; 119:3481-4; PMID:16931595; http://dx.doi.org/10.1242/jcs.03071
57. Schulze H, Dose M, Korpal M, Meyer I, Italiano JE Jr., Shivdasani RA. RanBP10 is a cytoplasmic guanine nucleotide exchange factor that modulates noncentrosomal microtubules. J Biol Chem 2008; 283:14109-19; PMID:18347012; http://dx.doi.org/10.1074/jbc.M709397200
58. Cheng H, Govindan JA, Greenstein D. Regulated trafficking of the MSP/Eph receptor during oocyte meiotic maturation in C. elegans. Curr Biol 2008; 18:705-14; PMID:18472420; http://dx.doi.org/10.1016/j.cub.2008.04.043
59. Yudin D, Fainzilber M. Ran on tracks–cytoplasmic roles for a nuclear regulator. J Cell Sci 2009; 122:587-93; PMID:19225125; http://dx.doi.org/10.1242/jcs.015289
60. Bischoff FR, Ponstingl H. Catalysis of guanine nucleotide exchange on Ran by the mitotic regulator RCC1. Nature 1991; 354:80-2; PMID:1944575; http://dx.doi.org/10.1038/354080a0
61. de Felipe KS, Pampou S, Jovanovic OS, Pericone CD, Ye SF, Kalachikov S, Shuman HA. Evidence for acquisition of Legionella type IV secretion substrates via interdomain horizontal gene transfer. J Bacteriol 2005; 187:7716-26; PMID:16267296; http://dx.doi.org/10.1128/JB.187.22.7716-7726.2005
62. de Felipe KS, Glover RT, Charpentier X, Anderson OR, Reyes M, Pericone CD, Shuman HA. Legionella eukaryotic-like type IV substrates interfere with organelle trafficking. PLoS Pathog 2008; 4:e1000117; PMID:18670632; http://dx.doi.org/10.1371/journal.ppat.1000117
63. Ninio S, Celli J, Roy CR. A Legionella pneumophila effector protein encoded in a region of genomic plasticity binds to Dot/Icm-modified vacuoles. PLoS Pathog 2009; 5:e1000278; PMID:19165328; http://dx.doi.org/10.1371/journal.ppat.1000278
64. Ivanov SS, Charron G, Hang HC, Roy CR. Lipidation by the host prenyltransferase machinery facilitates membrane localization of Legionella pneumophila effector proteins. J Biol Chem 2010; 285:34686-98; PMID:20813839; http://dx.doi.org/10.1074/jbc.M110.170746
65. Folly-Klan M, Alix E, Stalder D, Ray P, Duarte LV, Delprato A, Zeghouf M, Antonny B, Campanacci V, Roy CR, et al. A novel membrane sensor controls the localization and ArfGEF activity of bacterial RalF. PLoS Pathog 2013; 9:e1003747;PMID:24244168; http://dx.doi.org/10.1371/journal.ppat.1003747
66. Rothmeier E, Pfaffinger G, Hoffmann C, Harrison CF, Grabmayr H, Repnik U, Hannemann M, W€olke S, Bausch A, Griffiths G, et al. Activation of Ran GTPase by a Legionella effector promotes microtubule polymerization, pathogen vacuole motility and infection. PLoS Pathog 2013; 9:e1003598; PMID:24068924; http://dx.doi.org/10.1371/journal.ppat.1003598
67. Steggerda SM, Paschal BM. The mammalian Mog1 protein is a guanine nucleotide release factor for Ran. J Biol Chem 2000; 275:23175-80; PMID:10811801; http://dx.doi.org/10.1074/jbc.C000252200
68. Trulzsch K, Roggenkamp A, Aepfelbacher M, Wilharm G, Ruckdeschel K, Heesemann J. Analysis of chaperone-dependent Yop secretion/translocation and effector function using a mini-virulence plasmid of Yersinia enterocolitica. Int J Med Microbiol 2003; 293:167-77; PMID:12868653; http://dx.doi.org/10.1078/1438-4221-00251
69. Wolke S, Heesemann J. Probing the cellular effects of bacterial effector proteins with the Yersinia toolbox. Future Microbiol 2012; 7:449–56; PMID:22439722; http://dx.doi.org/10.2217/fmb.12.16
70. Rolando M, Sanulli S, Rusniok C, Gomez-Valero L, Bertholet C, Sahr T, Margueron R, Buchrieser C. Legionella pneumophila effector RomA uniquely modifies host chromatin to repress gene expression and promote intracellular bacterial replication. Cell Host Microbe 2013; 13:395-405; PMID:23601102; http://dx.doi.org/10.1016/j.chom.2013.03.004
71. Simon S, Wagner MA, Rothmeier E, Müller-Taubenberger A, Hilbi H. Icm/Dot-dependent inhibition of phagocyte migration by Legionella is antagonized by a translocated Ran GTPase activator. Cell Microbiol 2014; 16: 977-92; PMID:24397557