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Modulation of Rho GTPases by type III secretion system translocated effectors of Yersinia

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Reviews of Physiology, Biochemistry and Pharmacology

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 152))

Abstract

Pathogenic species of the bacterial genus Yersinia subdue the immune system to proliferate and spread within the host organism. For this purpose yersiniae employ a type III secretion apparatus which governs injection of six effector proteins (Y ersinia outer proteins; Yops) into host cells. Yops control various regulatory and signalling proteins in a unique and highly specific manner. YopE, YopT, and YpkA/YopO modulate the activity of Rho GTP-binding proteins, whereas YopH dephosphorylates phospho-tyrosine residues in focal adhesion proteins. Furthermore, YopP/YopJ and YopM affect cell survival/apoptosis and cell proliferation, respectively. In this review the focus will be on the biochemistry and cellular effects of YopT, YopE, YopO/YpkA, and YopH.

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References

  • Aepfelbacher M, Heesemann J (2001) Modulation of Rho GTPases and the actin cytoskeleton by Yersinia outer proteins (Yops). Int J Med Microbiol 291:269–276

    Article  PubMed  CAS  Google Scholar 

  • Aepfelbacher M, Trasak C, Wilharm G, Wiedemann A, Trulzsch K, Krauss K, Gierschik P, Heesemann J (2003) Characterization of YopT effects on Rho GTPases in Yersinia enterocolitica-infected cells. J Biol Chem 278:33217–33223

    Article  PubMed  CAS  Google Scholar 

  • Aili M, Telepnev M, Hallberg B, Wolf-Watz H, Rosqvist R (2003) In vitro GAP activity towards RhoA, Rac1 and Cdc42 is not a prerequisite for YopE-induced HeLa cell cytotoxicity. Microb Pathog 34:297–308

    Article  PubMed  CAS  Google Scholar 

  • Alonso A, Bottini N, Bruckner S, Rahmouni S, Williams S, Schoenberger SP, Mustelin R (2004) Lck Dephosphorylation at Tyr-394 and inhibition of T cell antigen receptor signaling by Yersinia Phosphatase YopH. J Biol Chem 279:4922–4928

    Article  PubMed  CAS  Google Scholar 

  • Alrutz MA, Srivastava A, Wong KW, D’Souza-Schorey C, Tang M, Ch’Ng LE, Snapper SB, Isberg RR (2001) Efficient uptake of Yersinia pseudotuberculosis via integrin receptors involves a Rac1-Arp 2/3 pathway that bypasses N-WASP function. Mol Microbiol 42:689–703

    Article  PubMed  CAS  Google Scholar 

  • Andor A, Trülzsch K, Essler M, Wiedemann A, Roggenkamp A, Heesemann J, Aepfelbacher M (2001) YopE of Yersinia, a GAP for Rho-GTPases, selectively modulates Rac-dependent actin structures in endothelial cells. Cell Microbiol 3:301–310

    Article  PubMed  CAS  Google Scholar 

  • Arbibe L, Mira JP, Teusch N, Kline L, Guha M, Mackman N, Godowski PJ, Ulevitch RJ, Knaus UG (2000) Toll-like receptor 2-mediated NF-kappa B activation requires a Rac1-dependent pathway. Nat Immunol 1:533–540

    Article  PubMed  CAS  Google Scholar 

  • Barz C, Abahji TN, Trülzsch K, Heesemann J (2000) The Yersinia Ser/Thr protein kinase YpkA/YopO directly interacts with the small GTPases RhoA and Rac-1. FEBS Lett 482:139–143

    Article  PubMed  CAS  Google Scholar 

  • Bishop AL, Hall A (2000) Rho GTPases and their effector proteins. Biochem J 348:241–255

    Article  PubMed  CAS  Google Scholar 

  • Black DS, Bliska JB (2000) The RhoGAP activity of the Yersinia pseudotuberculosis cytotoxin YopE is required for antiphagocytic function and virulence. Mol Microbiol 37:515–527

    Article  PubMed  CAS  Google Scholar 

  • Black DS, Bliska JB (1997) Identification of p130Cas as a substrate of Yersinia YopH (Yop51), a bacterial protein tyrosine phosphatase that translocates into mammalian cells and targets focal adhesions. EMBO J 16:2730–2744

    Article  PubMed  CAS  Google Scholar 

  • Black DS, Montagna LG, Zitsmann S, Bliska JB (1998) Identification of an amino-terminal substrate-binding domain in the Yersinia tyrosine phosphatase that is required for efficient recognition of focal adhesion targets. Mol Microbiol 29:1263–1274

    Article  PubMed  CAS  Google Scholar 

  • Bliska JB (2000) Yop effectors of Yersinia spp and actin rearrangements. Trends Microbiol 8:205–208

    Article  PubMed  CAS  Google Scholar 

  • Brakebusch C, Fässler R (2003) The integrin-actin connection, an eternal love affair. EMBO J 22:2324–2333

    Article  PubMed  CAS  Google Scholar 

  • Cornelis GR (2002) The Yersinia Ysc-Yop “Typ III” weaponry. Nat Rev Mol Cell Biol 3:742–752

    Article  PubMed  CAS  Google Scholar 

  • Cornelis GR, Wolf-Watz H (1997) The Yersinia Yop virulon: a bacterial system for subverting eukaryotic cells. Mol Microbiol 23:861–867

    Article  PubMed  CAS  Google Scholar 

  • Cornelis GR, Boland A, Boyd AP, Geuijen C, Iriarte M, Neyt C, Sory MP, Stainier I (1998) The virulence plasmid of Yersinia, an antihost genome. Microbiol Mol Biol Rev 62:1315–1352

    PubMed  CAS  Google Scholar 

  • Dukuzumuremyi JM, Rosqvist R, Hallberg B, Akerstrom B, Wolf-Watz H, Schesser K (2000) The Yersinia protein kinase A is a host-factor inducible RhoA/Rac-binding virulence factor. J Biol Chem 275:35281–35290

    Article  PubMed  CAS  Google Scholar 

  • El Tahir Y, Skurnik M (2001) YadA, the multifaceted Yersinia adhesin. Int J Med Microbiol 291:209–218

    Article  PubMed  Google Scholar 

  • Fällman M, Andersson K, Hakansson S, Magnusson KE, Stendahl O, Wolf-Watz H (1995) Yersinia pseudotuberculosis inhibits Fc receptor-mediated phagocytosis in J774 cells. Infect Immun 63:3117–3124

    PubMed  Google Scholar 

  • Fu Y, Galan JE (1999) A Salmonella protein antagonizes Rac-1 and Cdc42 to mediate host-cell recovery after bacterial invasion. Nature 401:293–297

    Article  PubMed  CAS  Google Scholar 

  • Galyov EE, Hakansson S, Forsberg A, Wolf Watz H (1993) A secreted protein kinase of Yersinia pseudotuberculosis is an indispensable virulence determinant. Nature 361:730–732

    Article  PubMed  CAS  Google Scholar 

  • Giancotti FG (2000) Complexity and specificity of integrin signalling. Nat Cell Biol 2:13–14

    Article  CAS  Google Scholar 

  • Goehring UM, Schmidt G, Pederson KJ, Aktories K, Barbieri JT (1999) The N-terminal domain of Pseudomonas aeruginosa exoenzyme S is a GTPase-activating protein for Rho GTPases. J Biol Chem 274:36369–36372

    Article  PubMed  CAS  Google Scholar 

  • Grosdent N, Maridonneau-Parini I, Sory MP, Cornelis GR (2002) Role of Yops and adhesins in resistance of Yersinia enterocolitica to phagocytosis. Infect Immun 70:4165–4176

    Article  PubMed  CAS  Google Scholar 

  • Hakansson S, Galyov EE, Rosqvist R, Wolf Watz H (1996) The Yersinia YpkA Ser/Thr kinase is translocated and subsequently targeted to the inner surface of the HeLa cell plasma membrane. Mol Microbiol 20:593–603

    Article  PubMed  CAS  Google Scholar 

  • Hamid N, Gustavsson A, Andersson K, McGee K, Persson C, Rudd CE, Fallman M (1999) YopH dephosphorylates Cas and Fyn-binding protein in macrophages. Microb Pathog 27:231–242

    Article  PubMed  CAS  Google Scholar 

  • Higgs HN, Pollard TD (1999) Regulation of actin polymerization by Arp2/3 complex and WASp/Scar proteins. J Biol Chem 274:3253–3254

    Article  Google Scholar 

  • Hoffmann C, Pop M, Leemhuis J, Schirmer J, Aktories K, Schmidt G (2004) The Yersinia pseudotuberculosis cytotoxic necrotizing factor (CNFY) selectively activates RhoA. J Biol Chem 279:16026–16032

    Article  PubMed  CAS  Google Scholar 

  • Hoiczyk E, Roggenkamp A, Reichenbecher M, Lupas A, Heesemann J (2000) Structure and sequence analysis of Yersinia YadA and Moraxella UspAs reveal a novel class of adhesins. EMBO J 19:5989–5999

    Article  PubMed  CAS  Google Scholar 

  • Hueck CJ (1998) Type III protein secretion systems in bacterial pathogens of animals and plants. Microbiol Mol Biol Rev 62:379–433

    PubMed  CAS  Google Scholar 

  • Iriarte M, Cornelis GR (1998) YopT, a new Yersinia effector protein, affects the cytoskeleton of host cells. Mol Microbiol 29:915–929

    Article  PubMed  CAS  Google Scholar 

  • Isberg RR, Leong JM (1990) Multiple beta 1 chain integrins are receptors for invasin, a protein that promotes bacterial penetration into mammalian cells. Cell 60:861–871

    Article  PubMed  CAS  Google Scholar 

  • Isberg RR, Hamburger Z, Dersch P (2000) Signaling and invasin-promoted uptake via integrin receptors. Microbes Infect 2:793–801

    Article  PubMed  CAS  Google Scholar 

  • Juris SJ, Rudolph AE, Huddler D, Orth K, Dixon JE (2000) A distinctive role for the Yersinia protein kinase: actin binding, kinase activation, and cytoskeleton disruption. Proc Natl Acad Sci 97:9431–9436

    Article  PubMed  CAS  Google Scholar 

  • Juris SJ, Shao F, Dixon FE (2002) Yersinia effectors target mammalian signalling pathways. Cell Microbiol 4:201–211

    Article  PubMed  CAS  Google Scholar 

  • Karin M, Lin A (2002) NF-kappaB at the crossroads of life and death. Nat Immunol 3:221–227

    Article  PubMed  CAS  Google Scholar 

  • Krall R, Zhang Y, Barbieri JT (2004) Intracellular membrane localization of pseudomonas ExoS and Yersinia YopE in mammalian cells. J Biol Chem 279:2747–2753

    Article  PubMed  CAS  Google Scholar 

  • Leung KY, Reisner BS, Straley SC (1990) YopM inhibits platelet aggregation and is necessary for virulence of Yersinia pestis in mice. Infect Immun 58:3262–3271

    PubMed  CAS  Google Scholar 

  • Lockman HA, Gillespie RA, Baker BD, Shakhnovich E (2002) Yersinia pseudotuberculosis produces a cytotoxic necrotizing factor. Infect Immun 70:2708–2714

    Article  PubMed  CAS  Google Scholar 

  • Logsdon LK, Mecsas J (2003) Requirement of the Yersinia pseudotuberculosis effectors YopH and YopE in colonization and persistence in intestinal and lymph tissues. Infect Immun 71:4595–4607

    Article  PubMed  CAS  Google Scholar 

  • McDonald C, Vacratsis PO, Bliska JB, Dixon JE (2003) The yersinia virulence factor YopM forms a novel protein complex with two cellular kinases. J Biol Chem 278:18514–18523

    Article  PubMed  CAS  Google Scholar 

  • McGee K, Zettl M, Way M, Fallman M (2001) A role for N-WASP in invasin-promoted internalisation. FEBS Lett 509:59–65

    Article  PubMed  CAS  Google Scholar 

  • Montagna LG, Ivanov MI, Bliska JB (2001) Identification of residues in the amino-terminal domain of the Yersinia tyrosine phosphatase that are critical for substrate recognition. J Biol Chem 276:5005–5011

    Article  PubMed  CAS  Google Scholar 

  • Moon SY, Zheng Y (2003) Rho GTPase-activating proteins in cell regulation. Trends Cell Biol 13:13–22

    Article  PubMed  CAS  Google Scholar 

  • Olofsson B (1999) Rho guanine dissociation inhibitors: pivotal molecules in cellular signalling. Cell Signal 11:545–554

    Article  PubMed  CAS  Google Scholar 

  • Orth K, Palmer LE, Bao ZQ, Stewart S, Rudolph AE, Bliska JB, Dixon JE (1999) Inhibition of the mitogen-activated protein kinase kinase superfamily by a Yersinia effector. Science 285:1920–1923

    Article  PubMed  CAS  Google Scholar 

  • Pawel-Rammingen von, U, Telepnev, MV, Schmidt, G, Aktories, K, Wolf-Watz, H, Rosqvist, R (2000) GAP activity of the Yersinia YopE cytotoxin specifically targets the Rho pathway: a mechanism for disruption of actin microfilament structure. Mol Microbiol 36:737–748

    Article  Google Scholar 

  • Persson C, Carballeira N, Wolf Watz H, Fallman M (1997) The PTPase YopH inhibits uptake of Yersinia, tyrosine phosphorylation of p130Cas and FAK, and the associated accumulation of these proteins in peripheral focal adhesions. EMBO J 16:2307–2318

    Article  PubMed  CAS  Google Scholar 

  • Persson C, Nordfelth R, Andersson K, Forsberg A, Wolf-Watz H, Fallman M (1999) Localization of the Yersinia PTPase to focal complexes is an important virulence mechanism. Mol Microbiol 33:828–838

    Article  PubMed  CAS  Google Scholar 

  • Ridley AJ, Self AJ, Kasmi F, Paterson HF, Hall A, Marshall CJ, Ellis C (1993) Rho family GTPase activating proteins p190, bcr and rhoGAP show distinct specificities in vitro and in vivo. EMBO J 12:5151–5160

    PubMed  CAS  Google Scholar 

  • Rosqvist R, Forsberg A, Wolf Watz H (1991) Intracellular targeting of the Yersinia YopE cytotoxin in mammalian cells induces actin microfilament disruption. Infect Immun 59:4562–4569

    PubMed  CAS  Google Scholar 

  • Rosqvist R, Bolin I, Wolf-Watz H (1998) Inhibition of phagocytosis in Yersinia pseudotuberculosis: a virulence plasmid-encoded ability involving the Yop2b protein. Infect Immun 56:2139–2143

    Google Scholar 

  • Ruckdeschel K (2002) Immunomodulation of macrophages by pathogenic Yersinia species. Arch Immunol Therap Exp 50:131–137

    CAS  Google Scholar 

  • Ruckdeschel K, Roggenkamp A, Schubert S, Heesemann J (1996) Differential contribution of Yersinia enterocolitica virulence factors to evasion of microbicidal action of neutrophils. Infect Immun 64:724–733

    PubMed  CAS  Google Scholar 

  • Ruckdeschel K, Mannel O, Richter K, Jacobi CA, Trulzsch K, Rouot B, Heesemann J (2001) Yersinia outer protein P of Yersinia enterocolitica simultaneously blocks the nuclear factor-kappaB pathway and exploits lipopolysaccharide signaling to trigger apoptosis in macrophages. J Immunol 166:1823–1831

    PubMed  CAS  Google Scholar 

  • Sauvonnet N, Pradet-Balade B, Garcia-Sanz JA, Cornelis GR (2002) Regulation of mRNA expression in macrophages after Yersinia enterocolitica infection. Role of different Yop effectors. J Biol Chem 277:25133–25142

    Article  PubMed  CAS  Google Scholar 

  • Scheffzek K, Ahmadian MR, Wittinghofer A (1998) GTPase-activating proteins: helping hands to complement an active site. Trends Biochem Sci 23:257–262

    Article  PubMed  CAS  Google Scholar 

  • Shao F, Merritt PM, Bao Z, Innes RW, Dixon JE (2002) A Yersinia effector and a Pseudomonas avirulence protein define a family of cysteine proteases functioning in bacterial pathogenesis. Cell 109:575–588

    Article  PubMed  CAS  Google Scholar 

  • Shao F, Vacratsis PO, Bao Z, Bowers KE, Fierke CA, Dixon JE (2003) Biochemical characterization of the Yersinia YopT protease: cleavage site and recognition elements in Rho GTPases. Proc Natl Acad Sci 100:904–909

    Article  PubMed  CAS  Google Scholar 

  • Skrzypek E, Cowan C, Straley SC (1998) Targeting of the Yersinia pestis YopM protein into HeLa cells and intracellular trafficking to the nucleus. Mol Microbiol 30:1051–1065

    Article  PubMed  CAS  Google Scholar 

  • Sorg I, Hoffmann C, Dumbach J, Aktories K, Schmidt G (2003) The C terminus of YopT is crucial for activity and the N terminus is crucial for substrate binding. Infect Immun 71:4623–4632

    Article  PubMed  CAS  Google Scholar 

  • Symons M, Settleman J (2000) Rho family GTPases: more than simple switches. Trends Cell Biol 10:415–419

    Article  PubMed  CAS  Google Scholar 

  • Van Aelst L, D’Souza-Schorey C (1997) Rho GTPases and signaling networks. Genes Dev 11:2295–2322

    Article  PubMed  Google Scholar 

  • Wiedemann A, Linder S, Grassl G, Albert M, Autenrieth I, Aepfelbacher M (2001) Yersinia enterocolitica invasin triggers phagocytosis via beta1 integrins, Cdc42Hs and WASp in macrophages. Cell Microbiol 3:693–702

    Article  PubMed  CAS  Google Scholar 

  • Wurtele M, Wolf E, Pederson KJ, Buchwald G, Ahmadian MR, Barbieri JT, Wittinghofer A (2001) How the Pseudomonas aeruginosa ExoS toxin downregulates Rac. Nat Struct Biol 8:23–26

    Article  PubMed  CAS  Google Scholar 

  • Zhu M, Shao F, Innes RW, Dixon JE, Xu Z (2004) The crystal structure of Pseudomonas avirulence protein AvrPphB: a papain-like fold with a distinct substrate-binding site. Proc Natl Acad Sci 101:302–307

    Article  PubMed  CAS  Google Scholar 

  • Zumbihl R, Aepfelbacher M, Andor A, Jacobi CA, Ruckdeschel K, Rouot B, Heesemann J (1999) The cytotoxin YopT of Yersinia enterocolitica induces modification and cellular redistribution of the small GTP-binding protein RhoA. J Biol Chem 274:29289–29293

    Article  PubMed  CAS  Google Scholar 

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  1. Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiogie, Pettenkoferstr. 9a, 80336, München, Germany

    M. Aepfelbacher

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Aepfelbacher, M. (2004). Modulation of Rho GTPases by type III secretion system translocated effectors of Yersinia . In: Reviews of Physiology, Biochemistry and Pharmacology. Reviews of Physiology, Biochemistry and Pharmacology, vol 152. Springer, Berlin, Heidelberg. https://doi.org/10.1007/s10254-004-0035-3

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