Skip to main content

Rho GTP-Binding Proteins as Targets for Microbial Pathogens

  • Chapter
Cytoskeleton and Small G Proteins

Abstract

Conceptual approaches in microbial pathogenesis studies have evolved quickly in the last 10 years, due to the development of cell biology. The merging of cell biology and microbial pathogenesis has been called cellular microbiology (Cossart et al. 1996), definitively sealing this seminal association.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abo A, Pick E, Hall A, Totty N, Teahan CG, Segal AW (1991) The small GTP-binding protein, p21 Rac, is involved in the activation of the phagocyte NADPH oxidase. Nature 353:668–670

    Article  PubMed  CAS  Google Scholar 

  • Adam T, Giry M, Boquet P, Sansonetti PJ (1996) Rho-dependent membrane folding causes Shigella entry into epithelial cells. EMBO J 15:3315–3321

    PubMed  CAS  Google Scholar 

  • Aktories K (1997) Bacterial toxins that target Rho proteins. J Clin Invest 99:827–829

    Article  PubMed  CAS  Google Scholar 

  • Allured VS, Collier RJ, Carrol SF, McKay DB (1986) Structure of exotoxin A of Pseudomonas aeruginosa at 3.0 Angstrom resolution. Proc Natl Acad Sci USA 83:1320–1324

    Article  PubMed  CAS  Google Scholar 

  • Amano M, Ito M, Kimura K, Fukata Y, Chihara K, Nakano T, Matsuura Y, Kaibuchi K (1996) Phosphorylation and activation of myosin by Rho-associated kinase (Rho-kinase). J Biol Chem 271:20246–20249

    Article  PubMed  CAS  Google Scholar 

  • Bagrodia S, Derijard B, Davis J, Cerione RA (1995) Cdc42 and PAK-mediated signalling leads to Jun kinase and p38 mitogen-activated protein kinase activation. J Biol Chem 270:27995–27998

    Article  PubMed  CAS  Google Scholar 

  • Blum G, Falbo V, Alonso MP, Blanco JE, Gonzales EA, Garabal JI (1995) Gene clusters encoding the cytotoxic necrotizing factor type 1 PRS fimbriae and a hemolysin from the pathogenicity island II of the uropathogenic Escherichia coli strain J96. FEMS Microbiol Lett 126:189–196

    PubMed  CAS  Google Scholar 

  • Braga VMM, Machesky LM, Hall A, Hotchin N (1997) The small GTPases Rho and Rac are required for the establishment of cadherin-dependent cell-cell contacts. J Cell Biol 137:1421–1431

    Article  PubMed  CAS  Google Scholar 

  • Caprioli A, Falbo V, Roda LG, Ruggeri FM, Zona C (1983) Partial purification and characterization of an Escherichia coli toxic factor that induces morphological cell alterations. Infect Immun 39:1300–1306

    PubMed  CAS  Google Scholar 

  • Chardin P, Boquet P, Madaule P, Popoff MR, Rubin EJ, Gill DM (1989) The mammalian G protein RhoC is ADPribosylated by Clostridium botulinum C3 and affects actin microfilaments in Vero cells. EMBO J 8:1087–1092

    PubMed  CAS  Google Scholar 

  • Chen LM, Hobbie S, Galan JE (1996) Requirement of Cdc42 for Salmonella-induced cytoskeletal and nuclear responses. Science 274:2115–2118

    Article  PubMed  CAS  Google Scholar 

  • Chrzanowska-Wodnicka M, Burridge K (1996) Rho-stimulated contractility drives the formation of stress fibers and focal adhesions. J Cell Biol 6:1403–1415

    Article  Google Scholar 

  • Collazo CM, Galan JE (1997) The invasion-associated type III system of Salmonella typhimurium directs the translocation of Sip proteins into the host cell. Mol Microbiol 24:747–756

    Article  PubMed  CAS  Google Scholar 

  • Cornelis G, 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 

  • Cossart P, Baquet P, Normark S, Rappuoli R (1996) Cellular microbiology emerging. Science 271:315–316

    Article  PubMed  CAS  Google Scholar 

  • De Rycke J, Guillot JF, Boivin R (1987) Cytotoxins in non-enterotoxigenic strains of Escherichia coli isolated from faeces of diarrheic calves. Vet Microbiol 15:137–157

    Article  PubMed  Google Scholar 

  • De Rycke J, Gonzalez EA, Blanco J, Oswald E, Blanco M, Boivin R (1990) Evidence for two types of cytotoxic necrotizing factor in human and animal clinical isolates. J Clin Microbiol 28:694–699

    PubMed  Google Scholar 

  • Donelli G, Fiorentini C, Falzano L, Pouchelet M, Oswald E, Boquet P (1994) Effects induced by the cytotoxic necrotizing factor 1 (CNF1) from pathogenic E. coli on cultured epithelial cells. Zentrabl Bakteriol Suppl 24:60–71

    CAS  Google Scholar 

  • Falbo V, Pace T, Picci L, Pizzi E, Caprioli A (1993) Isolation and nucleotide sequence of the gene encoding cytotoxic necrotizing factor type 1. Infect Immun 61:4909–4914

    PubMed  CAS  Google Scholar 

  • Falzano L, Fiorentini C, Donelli G, Michel E, Kocks C, Cossart P, Cabanié L, Oswald E, Baquet P (1993) Induction of phagocytic behaviour in human epithelial cells by Escherichia coli cytotoxic necrotizing factor 1. Mol Microbiol 9:1247–1254

    Article  PubMed  CAS  Google Scholar 

  • Finlay BB, Falkow S (1997) Common themes in microbial pathogenicity revisited. Mol Biol Rev 61:136–169

    CAS  Google Scholar 

  • Fiorentini C, Arancia G, Caprioli A, Falbo V, Ruggeri FM, Donelli G (1988) Cytoskeletal changes induced in HEp-2 cells by the cytotoxic necrotizing factor of Escherichia coli. Toxicon 26:1047–1056

    Article  PubMed  CAS  Google Scholar 

  • Fiorentini C, Giry M, Donelli G, Falzano L, Aullo P, Boquet P (1994) E. coli cytotoxic necrotizing factor 1 increases actin assembly via the p21 Rho GTPase. Zentrabl Bakteriol Suppl 24:404–405

    Google Scholar 

  • Fiorentini C, Donelli G, Matarrese P, Fabbri A, Paradisi S, Boquet P (1995) Escherichia coli cytotoxic necrotizing factor 1: evidence for induction of actin assembly by constitutive activation of the p21 Rho GTPase. Infect Immun 63:3936–3944

    PubMed  CAS  Google Scholar 

  • Flatau G, Lemichez E, Gauthier M, Chardin P, Paris S, Fiorentini C, Boquet P (1997) Toxin-induced activation of the G-protein Rho by deamidation of glutamine. Nature 387:729–733

    Article  PubMed  CAS  Google Scholar 

  • Fujihara H, Walker LA, Gong MC, Lemichez E, Boquet P, Somlyo AV, Somlyo AP (1997) Inhibition of RhoA translocation and calcium sensitivation by in vivo ADP-ribosylation of Rho with the chimeric DC3B. Mol Biol Cell 8:2437–2447

    PubMed  CAS  Google Scholar 

  • Genth H, Hofman F, Selzer J, Rex G, Aktories K, Just I (1996) Difference in protein substrates specificity between hemorrhagic toxin and lethal toxin from Clostridium sordellii. Biochem Biophys Res Comm 229:370–374

    Article  PubMed  CAS  Google Scholar 

  • Gilmore AP, Burridge K (1996) Regulation of vinculin binding to talin and actin by phosphatidylinositol 4–5 biphosphate. Nature 381:531–535

    Article  PubMed  CAS  Google Scholar 

  • Gong MC, Iizuka K, Nixon G, Browne JP, Hall A, Eccleston JF, Sugai M, Kobayashi S, Somlyo AV, Somlyo AP (1996) Role of guanine nucleotide binding proteins-Ras-family or trimeric proteins or both in Cat sensitization of smooth muscles. Proc Natl Acad Sci USA 93:1340–1345

    Article  PubMed  CAS  Google Scholar 

  • Hall A (1998) Rho GTPases and the actin cytoskeleton. Science 279:509–514

    Article  PubMed  CAS  Google Scholar 

  • Hartwig JH, Bokoch GM, Carpenter CL, Jeanmey PA, Taylor LA, Toker A, Stossel TP (1995) Thrombin receptor ligation and activated Rac uncap actin filament barbed ends through phosphoinositide synthesis in permeabilized human platelets. Cell 82:643–653

    Article  PubMed  CAS  Google Scholar 

  • Hermant D, Ménard R, Arricau N, Parsot C, Popoff MY (1995) Functional conservation of the Salmonella and Shigella effectors of entry into epithelial cells. Mol Microbiol 17:781–789

    Article  PubMed  CAS  Google Scholar 

  • Higley S, Way M (1997) Actin and cell pathogenesis. Curr Opin Cell Biol 9:62–69

    Article  PubMed  CAS  Google Scholar 

  • Hirao M, Sato N, Kondo T, Yonemura S, Monden M, Sasaki T, Takai Y, Tsukita S, Tsukita S (1996) Regulation mechanism of ERM (ezrin, radixin/moesin) protein/plasma association: possible involvement of phosphatidylinositol turnover and Rho-dependent signalling pathways. J Cell Biol 135:37–51

    Article  PubMed  CAS  Google Scholar 

  • Hofman F, Busch C, Prepens U, Just I, Aktories K (1997) Localization of the glucosyltransferase activity of Clostridium difficile toxin B to the N-terminal part of holotoxin. J Biol Chem 272:11074–11078

    Article  Google Scholar 

  • Horiguchi Y, Inoue N, Masuda M, Kashimoto T, Katahira J, Sugimoto N, Matsuda M (1997) Bordetella bronchiseptica dermonecrotizing toxin induces reorganization of actin stress fibers through deamidation of Gln-63 of the GTP-binding Rho. Proc Natl Acad Sci USA 94:11623–11626

    Article  PubMed  CAS  Google Scholar 

  • Isberg RR (1991) Discrimination between intracellular uptake and surface adhesion of bacterial pathogens. Science 252:934–938

    Article  PubMed  CAS  Google Scholar 

  • Ishizaki T, Maekawa M, Fujisawa K, Okawa K, Iwamatsu A, Fujita A, Watanabe N, Saito Y, Kakizuka Y, Morii N, Narumiya S (1996) The small GTP-binding protein Rho binds to and activates a 160 kDa ser/thr protein kinase homologous to myotonic dystrophy kinase. FMB() J 15:1885–1893

    CAS  Google Scholar 

  • Jalink K, van Gorven EJ, Hengeveld T, Morii N, Narumiya S, Moolenar WH (1994) Inhibition of lysophosphatidate-and thrombin-induced neurite retraction and neuronal cell rounding by ADP-ribosylation of the small GTP-binding protein Rho. J Cell Biol 126:801–810

    Article  PubMed  CAS  Google Scholar 

  • Jones BD, Paterson HF, Hall A, Falkow S (1993) Salmonella typhimurium induces membrane ruffling by a growth-factor receptor independent mechanism. Proc Natl Acad Sci USA 90:10390–10394

    Article  PubMed  CAS  Google Scholar 

  • Just I, Selzer J, Wilm M, von Eichel-Streiber C, Mann M, Aktories K (1995a) Glucosylation of Rho proteins by Clostridium difficile toxin B. Nature 375:500–503

    Article  PubMed  CAS  Google Scholar 

  • Just I, Wilm M, Selzer J, Rex G, von Eichel-Streiber C, Mann M, Aktories K (1995b) The entero-toxin from Clostridium difficile (Tox A) monoglucosylates the Rho proteins. J Biol Chem 270:13932–13936

    Article  PubMed  CAS  Google Scholar 

  • Just I, Selzer J, Hofman F, Green GA, Aktories K (1996) Inactivation of Ras by Clostridium sordellii lethal toxin-catalyzed glucosylation. J Biol Chem 271:10217–10224.

    Article  Google Scholar 

  • Kimura K, Ito M, Amano M, Chihara K, Fukuta Y, Nakafuku M, Yamamori B, Feng J, Nakano T, Okawa K, Iwamatsu A, Kaibuchi K (1996) Regulation of myosin phosphatase by Rho and Rho-associated kinases (Rho-kinase). Science 273:245–247

    Article  PubMed  CAS  Google Scholar 

  • Kozma R, Ahmed S, Best A, Lim L (1996) The GTPase-activating protein n-chimerin cooperates with Rac1 and Cdc42Hs to induce the formation of lammelipodia and filopodia. Mol Cell Biol 16:5069–5080

    PubMed  CAS  Google Scholar 

  • Lamarche N, Tapon N, Stowers L, Burbelo PD, Aspenström P, Bridges T, Chan J, Hall A (1996) Rac and Cdc42 induce actin polymerization and G1 cell cycle progression independently of p65PAK and the JNK/SAPK MAP kinase cascade. Cell 87:519–529

    Article  PubMed  CAS  Google Scholar 

  • Lemichez E, Flatau G, Bruzzone M, Boquet P, Gauthier M (1997) Molecular localization of the Escherichia coli cytotoxic necrotizing factor CNF1 cell-binding and catalytic domains. Mol Microbiol 24:1061–1070

    Article  PubMed  CAS  Google Scholar 

  • MacKay DJG, Esch F, Furthmayr H, Hall A (1997) Rho-and Rac-dependent assembly of focal adhesion complexes and actin filaments in permeabilized fibroblasts: an essential role for ezrin/radixin/moesin proteins. J Cell Biol 138:927–938

    Article  PubMed  CAS  Google Scholar 

  • Madara JL (1988) Tight junction dynamics: is paracellular transport regulated? Cell 53:497–498

    Article  PubMed  CAS  Google Scholar 

  • Matsui T, Amano M, Yamamoto T, Chihara K, Nakafuku M, Ito M, Nakano T, Okawa K, Iwamatsu A, Kaibuchi K (1996) Rho-associated kinase, a novel serine/threonine kinase, as a putative target for the small GTP-binding protein Rho. EMBO J 15:2208–2216

    PubMed  CAS  Google Scholar 

  • Mengaud J, Ohayon H, Gounon P, Mège RM, Cossart P (1996) E-cadherin is the receptor for internalin, a surface protein required for entry of L. monocytogenes into epithelial cells. Cell 84:923–933

    Article  PubMed  CAS  Google Scholar 

  • Nobes CD, Hall A (1995) Rho, Rac and Cdc42 GTPases regulate the assembly of multi-molecular focal complexes associated with actin stress fibres, lammelipodia and filopodia. Cell 81:53–62

    Article  PubMed  CAS  Google Scholar 

  • Nusrat A, Giry M, Turner JR, Colgan SP, Parkos CA, Carnes D, Lemichez E, Boquet P, Madara JL (1995) Rho protein regulates tight junctions and perijunctional actin organization in polarized epithelia. Proc Natl Acad Sci USA 92:10629–10633

    Article  PubMed  CAS  Google Scholar 

  • Oswald E, Sugai M, Labigne A, Wu HC, Fiorentini C, Boquet P, O’Brien A (1994) Cytotoxic necrotizing factor type 2 produced by virulent Escherichia coli modifies the small GTPbinding protein Rho involved in assembly of actin stress fibers. Proc Natl Acad Sci USA 91:3814–3818

    Article  PubMed  CAS  Google Scholar 

  • Parsot C, Sansonetti PJ (1996) Invasion and the pathogenesis of Shigella infections. In: Miller VL (ed) Bacterial invasiveness. Springer, Berlin Heidelberg New York, pp 25–42

    Chapter  Google Scholar 

  • Paterson HF, Self AJ, Garrett MD, Just I, Aktories K, Hall A (1990) Microinjection of recombinant p21Rho induces rapid changes in cell morphology. J Cell Biol 111:1001–1007

    Article  PubMed  CAS  Google Scholar 

  • Popoff MR (1987) Purification and characterization of Clostridium sordellii lethal toxin and cross reactivity with Clostridium difficile cytotoxin. Infect Immun 55:35–43

    PubMed  CAS  Google Scholar 

  • Popoff MR, Chaves-Olarte E, Lemichez E, von Eichel-Streiber C, Thelestam M, Chardin P, Cussac D, Antonny B, Chavrier P, Flatau G, Boquet P (1996) Ras, Rap and Rac small GTP-binding proteins are targets for Clostridium sordellii lethal toxin glucosylation. J Biol Chem 271: 10217–10224

    Article  PubMed  CAS  Google Scholar 

  • Pothoulakis C, Gilbert RJ, Cladaras C, Castagliuolo I, Semenza G, Hitti Y, Moncrief JS, Linevsky J, Kelly CP, Nikulasson S, Lamont T (1996) Rabbit sucrase isomaltase contains a functional intestinal receptor for Clostridium difficile toxin A. J Clin Invest 98:641–649

    Article  PubMed  CAS  Google Scholar 

  • Ridley AJ, Hall A (1992) The small GTP-binding protein Rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors. Cell 70:389–399

    Article  PubMed  CAS  Google Scholar 

  • Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A (1992) The small GTP-binding protein Rac regulates growth factor-induced membrane ruffling. Cell 70:401–410

    Article  PubMed  CAS  Google Scholar 

  • Rittinger K, Walker PA, Eccleston JF, Smerdon SJ, Gamblin SJ (1997) Structure at 1.65 Angstom of RhoA and its GTPase-activating protein in complex with a transition state analog. Nature 389:758–762

    Article  PubMed  CAS  Google Scholar 

  • Rosenshine I, Ruschkowski S, Stein M, Reinscheid DJ, Mills SD, Finlay BB (1996) A pathogenic bacterium triggers epithelial cell signals to form a functional bacterial receptor that mediates actin pseudopod formation. EMBO J 15:2613–2624

    PubMed  CAS  Google Scholar 

  • Rubin EJ, Gill DM, Boquet P, Popoff MR (1988) Functional modification of a 21-kiloDalton G protein when ADP-ribosylated by exoenzyme C3 of Clostridium botulinum. Mol Cell Biol 8:418–426

    PubMed  CAS  Google Scholar 

  • Schmidt G, Sehr P, Wilm M, Selzer J, Mann M, Aktories K (1997) Gln 63 of Rho is deamidated by Escherichia coli cytotoxic necrotizing factor 1. Nature 387:725–728

    Article  PubMed  CAS  Google Scholar 

  • Sears CL, Kaper JB (1996) Enteric bacterial toxins: mechanisms of action and linkage to intestinal secretion. Microbiol Rev 60:167–215

    PubMed  CAS  Google Scholar 

  • Segal DE, Falkow S, Tompkins LS (1996) Helicobacter pylori attachment to gastric cells induces cytoskeletal rearrangements and tyrosine phosphorylation of host cell proteins. Proc Natl Acad Sci USA 93:1259–1264

    Article  PubMed  CAS  Google Scholar 

  • Sekine A, Fujiwara M, Narumiya S (1989) Asparagine residue in the Rho gene product is the modification site for botulinum ADP-ribosyltransferase. J Biol Chem 264:8602–8605

    PubMed  CAS  Google Scholar 

  • Selzer J, Hoffman F, Rex G, Wilm M, Mann M, Just I, Aktories K (1996) Clostridium novyi alphatoxin-catalyzed incorporation of GlcNAc into Rho subfamily proteins. J Biol Chem 271: 25173–25177

    Article  PubMed  CAS  Google Scholar 

  • Stasia MJ, Jouan A, Bourmeyester N, Boquet P, Vignais P (1991) ADP-ribosylation of a small size GTP-binding protein in bovine neutrophils by the C3 exoenzyme of Clostridium botulinum and effect on cell motility. Biochem Biophys Res Comm 180:615–622

    Article  PubMed  CAS  Google Scholar 

  • Swenson DL, Bukanov NO, Berg DE, Welch RA (1996) Two pathogenicity islands in uropathogenic Escherichia coli J96: cosmid cloning and sample sequencing. Infect Immun 64:3736–3743

    PubMed  CAS  Google Scholar 

  • Takaishi K, Sasaki T, Kotani H, Nishioka H, Takai Y (1997) Regulation of cell-cell adhesion by Rac and Rho small G proteins in MDCK cells. J Cell Biol 139:1047–1059

    Article  PubMed  CAS  Google Scholar 

  • Thelestam M, Florin I, Chaves-Olartes E (1997) Clostridium difficile toxins. In: Aktories K (ed) Bacterial toxins. Tools in cell biology and pharmacology. Chapman and Hall, Weinheim, pp 131–141

    Google Scholar 

  • Tran Van Nhieu G, Ben Ze’ev A, Sansonetti PJ (1997) Modulation of bacterial entry into epithelial cells by association between vinculin and the Shigella IpaA invasin. EMBO J 16:2717–2729

    Article  Google Scholar 

  • Tsukita S, Yonemura S, Tsukita S (1997) ERM proteins: head-to-tail regulation of actin-plasma membrane interaction. Trends Biochem Sci 22:53–58

    Article  PubMed  CAS  Google Scholar 

  • Von Eichel-Streiber C, Boquet P, Sauerborn M, Thelestam M (1996) Large clostridial cytotoxins - a family of glycosyltransferases modifying small GTP-binding proteins. Trends Microbiol 375:375–382

    Article  Google Scholar 

  • Walker KE, Weiss AA (1994) Characterization of the dermonecrotic toxin in the members of the genus Bordetella. Infect Immun 62:3817–3828

    PubMed  CAS  Google Scholar 

  • Watarai M, Funato S, Sasakawa S (1996) Interaction of Ipa proteins of Shigellaflexneri with α5ß1 integrin promotes entry of the bacteria into mammalian cells. J Exp Med 183:991–999

    Article  PubMed  CAS  Google Scholar 

  • Watarai M, Kamata Y, Kozaki S, Sasakawa C (1997) Rho, a small GTP-binding protein, is essential for Shigella invasion of epithelial cells. J Exp Med 185:281–292

    Article  PubMed  CAS  Google Scholar 

  • Wittinghofer A, Nassar N (1996) How ras-related proteins talk to their effectors. Trends Biochem Sci 21:488–491

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1999 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Boguet, P., Sansonetti, P.J., Van Nhieu, G.T. (1999). Rho GTP-Binding Proteins as Targets for Microbial Pathogens. In: Jeanteur, P. (eds) Cytoskeleton and Small G Proteins. Progress in Molecular and Subcellular Biology, vol 22. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-58591-3_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-58591-3_9

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-63659-2

  • Online ISBN: 978-3-642-58591-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics