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Clostridial ADP-ribosyltransferases — Modification of low molecular weight GTP-binding proteins and of actin by clostridial toxins

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References

  • Adam-Vizi V, Rösener S, Aktories K, Knight DE (1988) Botulinum toxin-induced ADP-ribosylation and inhibition of exocytosis are unrelated events. FEBS Lett 238:277–280

    Google Scholar 

  • Adari H, Lowy DR, Willumsen BM, der Channing J, McCormick F (1988) Guanosine triphosphate-activating protein (GAP) interacts with the p21 ras effector binding domain. Science 240:518–521

    Google Scholar 

  • Aktories K, Frevert J (1987) ADP-ribosylation of a 21–24 kDa eukaryotic protein(s) by C3, a novel botulinum ADP-ribosyltransferase, is regulated by guanine nucleotide. Biochem J 247:363–368

    Google Scholar 

  • Aktories K, Wegner A (1989) ADP-ribosylation of actin by clostridial toxins. J Cell Biol 109:1385–1387

    Google Scholar 

  • Aktories K, Bärmann M, Ohishi I, Tsuyama S, Jakobs KH, Habermann E (1986a) Botulinum C2 toxin ADP-ribosylates actin. Nature 322:390–392

    CAS  PubMed  Google Scholar 

  • Aktories K, Ankenbauer T, Schering B, Jakobs KH (1986b) ADP-ribosylation of platelet actin by botulinum C2 toxin. Eur J Biochem 161:155–162

    Google Scholar 

  • Aktories K, Weller U, Chhatwal GS (1987) Clostridium botulinum type C produces a novel ADP-ribosyltransferase distinct from botulinum C2 toxin. FEBS Lett 212:109–113

    Google Scholar 

  • Aktories K, Rösener S, Blaschke U, Chhatwal GS (1988a) Botulinum ADP-ribosyltransferase C3. Purification of the enzyme and characterization of the ADP-ribosylation reaction in platelet membranes. Eur J Biochem 172:445–450

    Google Scholar 

  • Aktories K, Just I, Rosenthal W (1988b). Different types of ADP-ribose protein bonds formed by botulinum C2 toxin, botulinum ADP-ribosyltransferase C3 and pertussis toxin. Biochem Biophys Res Commun 156:361–367

    Google Scholar 

  • Aktories K, Braun U, Rösener S, Just I, Hall A (1989a) The rho gene product expressed in E. coli is a substrate of botulinum ADP-ribosyltransferase C3. Biochem Biophys Res Commun 158:209–213

    Google Scholar 

  • Aktories K, Reuner K-H, Presek P, Bärmann M (1989b) Botulinum C2 toxin treatment increases the G-actin pool in intact chicken cells: a model for the cytopathic action of actin-ADP-ribosylating toxins. Toxicon 27:989–993

    Google Scholar 

  • Al-Mohanna FA, Ohishi I, Hallett MB (1987) Botulinum C2 toxin potentiates activation of the neutrophil oxidase. FEBS Lett 219:40–44

    Google Scholar 

  • Althaus FR, Richter C (1987) ADP-ribosylation of proteins. Mol Biol Biochem Biophys 37:1–237

    Google Scholar 

  • Barbacid M (1987) ras Genes. Annu Rev Biochem 56:779–827

    Google Scholar 

  • Bokoch GM, Katada T, Northup JK, Hewlett EL, Gilman AG (1983) Identification of the predominant substrate for ADP-ribosylation by islet activating protein. J Biol Chem 258:2072–2075

    Google Scholar 

  • Böttinger H, Reuner KH, Aktories K (1987) Inhibition of histamine release from rat mast cells by botulinum C2 toxin. Int Arch Allergy Appl Immunol 84:380–384

    Google Scholar 

  • Braun U, Habermann B, Just I, Aktories K, Vandekerckhove J (1989) Purification of the 22-kDa protein substrate of botulinum ADP-ribosyltransferase C3 from porcine brain cytosol and its characterization as a GTP-binding protein highly homologous to the rho gene product. FEBS Lett 243:70–76

    Google Scholar 

  • Burns DL, Hewlett EL, Moss J, Vaughan M (1983) Pertussis toxin inhibits enkephalin stimulation of GTPase of NG108–15 cells. J Biol Chem 258:1435–1438

    Google Scholar 

  • Cassel D, Pfeuffer T (1978) Mechanism of cholera toxin action: covalent modification of the guanyl nucleotide-binding protein of the adenylate cyclase system. Proc Natl Acad Sci USA 75:2669–2673

    Google Scholar 

  • Cassel D, Selinger Z (1977) Mechanism of adenylate cyclase activation by cholera toxin: inhibition of GTP hydrolysis at the regulatory site. Proc Natl Acad Sci USA 74:3307–3311

    Google Scholar 

  • Chardin P, Tavitian A (1986) The ral gene: a new ras-related gene isolated by the use of a synthetic probe. EMBO J 5:2203–2208

    Google Scholar 

  • Chardin P, Madaule P, Tavitian A (1988) Coding sequence of human rho cDNAs clone 6 and clone 9. Nucleic Acids Res 16:2717

    Google Scholar 

  • Chardin P, Boquet P, Madaule P, Popoff MR, Rubin EJ, Gill DM (1989) The mammalian G protein rho C is ADP-ribosylated by Clostridium botulinum exoenzyme C3 and affects actin microfilament in Vero cells. EMBO J 8:1087–1092

    Google Scholar 

  • Coburn J, Dillon ST, Iglewski BH, Gill DM (1989a) Exoenzyme S of Pseudomonas aeruginosa ADP-ribosylates the intermediate filament protein vimentin. Infect Immun 57:996–998

    CAS  PubMed  Google Scholar 

  • Coburn J, Wyatt RT, Iglewsky BH, Gill DM (1989b) Several GTP-binding proteins, including p21c-H-ras, are perferred substrates of Pseudomonas aeruginosa exoenzyme S. J Biol Chem 264:9004–9008

    CAS  PubMed  Google Scholar 

  • Collier RJ (1982) Structure and activity of diphtheria toxin. In: Hayaishi O, Ueda K (eds) ADP ribosylation reactions. Academic press, New York, pp 575–592

    Google Scholar 

  • Cooper JM (1987) Effects of cytochalasin and phalloidin on actin. J Cell Biol 105:1473–1478

    Google Scholar 

  • Didsbury J, Weber RF, Bokoch GM, Evans T, Snyderman R (1989) rac, a novel ras-related family of proteins that are botulinum toxin substrates. J Biol Chem 264:16378–16382

    Google Scholar 

  • Eklund MW, Poysky FT, Reed SM, Smith CA (1971) Bacteriophage and the toxigenicity of Clostridium botulinum type C. Science 172:480–482

    Google Scholar 

  • Fuji N, Oguma K, Yokosawa N, Kimura K, Tsuzuki K (1988) Characterization of bacteriophage nucleic acids obtained from Clostridium botulinum types C and D. Appl Environ Microbiol 54:69–73

    Google Scholar 

  • Garrett MD, Self AJ, v.Oers C, Hall A (1989) Identification of distinct cytoplasmic targets for ras R-ras and rho regulatory proteins. J Biol Chem 264:10–13

    Google Scholar 

  • Geipel U, Just I, Schering B, Haas D, Aktories K (1989) ADP-ribosylation of actin causes increase in the rate of ATP exchange and inhibition of ATP-hydrolysis. Eur J Biochem 179:229–232

    Google Scholar 

  • Geipel U, Just I, Aktories K (1990) Inhibition of cytochalasin D-stimulated G-actin ATPase by ADP-ribosylation with Clostridium perfringens iota toxin. Biochem J 266:335–339

    Google Scholar 

  • Gill DM (1982) Cholera toxin-catalyzed ADP-ribosylation of membrane proteins. In: Hayaishi O, Ueda K (eds) ADP-ribosylation reactions. Academic press, New York, pp 593–645

    Google Scholar 

  • Gill DM, Richardson SH (1980) Adenosine diphosphate — ribosylation of adenylate catalyzed by heat — labile enterotoxin of Escherichia coli: comparison with cholera toxin. J Infect Dis 141:64–70

    Google Scholar 

  • Gill DM, Evans DJ Jr, Evans DG (1976) Mechanism of activation of adenylate cyclase in vitro by polymyxin-released, heat-labile enterotoxin of Escherichia coli. J Infect Dis 133 [Suppl 1]:S103-S107

    Google Scholar 

  • Habermann E, Dreyer F (1986) Clostridial neurotoxins: handling and action at the cellular and molecular level. Curr Top Microbiol Immunol 129:93–179

    Google Scholar 

  • Hsia JA, Tsai S-C, Adamik R, Yost DA, Hewlett EL, Moss J (1985) Amino acid-specific ADP-ribosylation. J Biol Chem 260:16187–16191

    Google Scholar 

  • Haubruck H, Disela C, Wagner P, Gallwitz D (1987) The ras-related ypt protein is an ubiquitous eukaryotic protein: isolation and sequence analysis of mouse cDNA clones highly homologous to the yeast YPTI gene. Embo J 6:4049–4053

    Google Scholar 

  • Honjo T, Nishizuka Y, Hayaishi O, Kato I (1968) Diphtheria-toxin-dependent-adenosine diphosphate ribosylation of aminoacyl transferase II and inhibition of protein synthesis. J Biol Chem 243:2553–3555

    Google Scholar 

  • Iglewski BH, Kabat D (1975) NAD-dependent inhibition of protein synthesis by Pseudomonas aeruginosa toxin. Proc Natl Acad Sci USA 72:2284–2289

    Google Scholar 

  • Jacquemin C, Thibout H, Lambert B, Correze C (1986) Endogenous ADP-ribosylation of Gs subunit and autonomous regulation and adenylate cyclase. Nature 323:182–184

    Google Scholar 

  • Just I, Geipel U, Aktories K (1989) ADP-ribosylation of actin by clostridial toxins. Reversible inhibition of actin ATPase. Naunyn Schmiedeberg's Arch Pharmacol [Suppl II] 340:R76

    Google Scholar 

  • Kikuchi A, Yamamoto K, Fujita T, Takai Y (1988) ADP-ribosylation of the bovine brain rho protein by botulinum toxin type C1. J Biol Chem 263:16303–16308

    Google Scholar 

  • Korn ED (1982) Actin polymerization and its regulation by proteins from nonmuscle cells. Physiol Rev 62:672–737

    Google Scholar 

  • Korn ED, Carlier MF, Pantaloni D (1987) Actin polymerization and ATP hydrolysis. Science 238:638–644

    Google Scholar 

  • Lee H, Iglewski WJ (1984) Cellular ADP-ribosylation with the same mechanism of action as diphtheria toxin and Pseudomonas toxin A. Proc Natl Acad Sci USA 81:2703–2707

    Google Scholar 

  • Leppla SH (1982) Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations in eukaryotic cells. Proc Natl Acad Sci USA 79:3162–3166

    CAS  PubMed  Google Scholar 

  • Madaule P, Axel R (1985) A novel ras-related gene family. Cell 41:31–40

    Google Scholar 

  • Madaule P, Axel R, Myers AM (1987) Characterization of two members of the rho gene family from the yeast Saccharomyces cerevisiae. Proc Natl Acad Sci USA 84:779–783

    Google Scholar 

  • Maller JL, Krebs EG (1977) Progesterone-stimulated meiotic cell division in Xenopus oocytes. J Biol Chem 252:1712–1718

    Google Scholar 

  • Matter K, Dreyer F, Aktories K (1989) Actin involvement in exocytosis from PC12 cells: studies on the influence of botulinum C2 toxin on stimulated noradrenaline release. J Neurochem 52:370–376

    Google Scholar 

  • Mauss S, Koch G, Kreye VAW, Aktories K (1989) Inhibition of the contraction of the isolated longitudinal muscle of the guinea-pig ileum by botulinum C2 toxin: evidence for a role of G/ F-actin transition in smooth muscle contraction. Naunyn Schmiedeberg's Arch Pharmacol 340:345–351

    Google Scholar 

  • Mauss S, Chaponnier C, Gabbiani G (1990) ADP-ribosylation of actin isoforms by botulinum C2 toxin and perfringens iota toxin. Naunyn Schmiedeberg's Arch Pharmacol [Suppl] 431:R33

    Google Scholar 

  • Mayer T, Koch R, Fanick W, Hilz H (1988) ADP-ribosyl proteins formed by pertussis toxin are specifically cleaved by mercury ions. Biol Chem Hoppe Seyler 369:579–583

    Google Scholar 

  • McCormick F (1989) Gasp: not just another oncogene. Nature 340:678–679

    Google Scholar 

  • Narumiya S, Sekine A, Fujiwara M (1988) Substrate for botulinum ADP-ribosyltransferase, Gb, has an amino acid sequence homologous to a putative rho gene product. J Biol Chem 263:17255–17257

    Google Scholar 

  • Noda M, Kato I, Matsuda F, Hirayama T (1981) Mode of action of staphylococcal leukocidin: relationship between binding of 125I-labeled S and F components of leukocidin to rabbit polymorphnuclear leukocytes and leukocidin activity. Infect Immun 34:362–367

    Google Scholar 

  • Norgauer J, Kownatzki E, Seifert R, Aktories K (1988) Botulinum C2 toxin ADP-ribosylates actin and enhances O2-production and secretion but inhibits migration of activated human neutrophils. J Clin Invest 82:1376–1382

    Google Scholar 

  • Norgauer J, Just I, Aktories K, Sklar LA (1989) Influence of botulinum C2 toxin on F-actin and N-formyl peptide receptor dynamics in human neutrophils. J Cell Biol 109:1133–1140

    Google Scholar 

  • Ohishi I (1983a) Response of mouse intestinal loop to botulinum C2 toxin: enterotoxic activity induced by cooperation of nonlinked protein components. Infect Immun 40:691–695

    Google Scholar 

  • Ohishi I (1983b) lethal and vascular permeability activities of botulinum C2 toxin induced by separate injection of the two toxin components. Infect Immun 40:336–339

    Google Scholar 

  • Ohishi I (1987) Activation of botulinum C2 toxin by trypsin. Infect Immun 55:1461–1465

    CAS  PubMed  Google Scholar 

  • Ohishi I, Odagiri Y (1984) Histopathological effect of botulinum C2 toxin on mouse intestines. Infect Immun 43:54–58

    CAS  PubMed  Google Scholar 

  • Ohishi I, Iwasaki M, Sakaguchi G (1980) Purification and characterization of two components of botulinum C2 toxin. Infect Immun 30:668–673

    CAS  PubMed  Google Scholar 

  • Ohishi I, Miyake M, Ogura K, Nakamura S (1984) Cytopathic effect of botulinum C2 toxin on tissue — culture cell lines. FEMS Microbiol Lett 23:281–284

    Google Scholar 

  • Pai EF, Kabsch W, Krengel U, Holmes KC, John J, Wittinghofer A (1989) Structure of the guanine nucleotide-binding domain of the Ha-ras oncogene product p21 in the triphosphate conformation. Nature 341:209–214

    Google Scholar 

  • Paterson HF, Self AJ, Garrett MD, Just I, Aktories K, Hall A (1990) Microinjection of recombinant p21-rho induces rapid changes in cell morphology. J Cell Biol (in press)

  • Pfeuffer T, Helmreich EJM (1988) Structural and functional relationship of guanosine triphosphate binding proteins. Curr Top Cell Regul 29:129–216

    Google Scholar 

  • Pizon V, Chardin P, Lerosey I, Olofson B, Tavitian A (1988) Human cDNAs rap 1 and rap 2 homologous to the Drosophila gene Dras3 encode proteins closely related to ras in the “effector” region. Oncogene 3:201–204

    Google Scholar 

  • Pollard T, Cooper JA (1986) Actin and actin-binding proteins. A critical evaluation of mechanism and functions. Annu Rev Biochem 55:987–1035

    Google Scholar 

  • Popoff MR, Boquet P (1988) Clostridium spiroforme toxin is a binary toxin which ADP-ribosylates cellular actin. Biochem Biophys Res Commun 152:1361–1368

    Google Scholar 

  • Popoff MR, Rubin EJ, Gill DM, Boquet P (1988) Actin-specific ADP-ribosyltransferase produced by a Clostridium difficile strain. Infect Immun 56:2299–2306

    CAS  PubMed  Google Scholar 

  • Reddy E, Reynolds R, Santos E, Barbacid (1982) A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene. Nature 300:149–152

    Google Scholar 

  • Reuner KH, Presek P, Boschek CB, Aktories K (1987) Botulinum C2 toxin ADP-ribosylates actin and disorganizes the microfilament network in intact cells. Eur J Cell Biol 43:134–140

    Google Scholar 

  • Rösener S, Chhatwal GS, Aktories K (1987) Botulinum ADP-ribosyltransferase C3 but not botulinum neurotoxins C1 and D ADP-ribosylates low molecular mass GTP-binding proteins. FEBS Lett 224:38–42

    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

    CAS  PubMed  Google Scholar 

  • Schering B, Bärmann M, Chhatwal GS, Geipel U, Aktories K (1988) ADP-ribosylation of skeletal muscle and non-muscle actin by Clostridium perfringens iota toxin. Eur J Biochem 171:225–229

    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

    CAS  PubMed  Google Scholar 

  • Simpson LL (1984) Molecular basis for the pharmacological actions of Clostridium Botulinum type C2 toxin. J Pharmacol Exp Ther 230:665–669

    CAS  PubMed  Google Scholar 

  • Simpson LL (1989) The binary toxin produced by Clostridium botulinum enters cells by receptor-mediated endocytosis to exert its pharmacologic effects. J Pharmacol Exp Ther 251:1223–1228

    CAS  PubMed  Google Scholar 

  • Simpson LL, Stiles BG, Zepeda HH, Wilkins TD (1987) Molecular basis for the pathological actions of Clostridium perfringens Iota toxin. Infect Immun 55:118–122

    Google Scholar 

  • Simpson LL, Stiles BG, Zepeda H, Wilkins TD (1989) Production by Clostridium spiroforme of an iotalike toxin that possesses mono(ADP-ribosyl)transferase activity: identification of a novel class of ADP-ribosyltransferases. Infect Immun 57:255–261

    Google Scholar 

  • Stiles BG, Wilkins TD (1986) Purification and characterization of Clostridium perfringens iota toxin: dependence on two nonlinked proteins for biological activity. Infect Immun 54:6783–688

    Google Scholar 

  • Stryer L, Bourne LR (1986) G proteins: a family of signal transducers. Annu Rev Cell Biol 2:391–419

    Google Scholar 

  • Tamura M, Nogimuri K, Murai S, Yajima M, Ito K, Katada T, Ui M, Ishii S (1982) Subunit structure of islet-activating protein, pertussis toxin, in conformity with the A-B model. Biochemistry 21:5516–5522

    Google Scholar 

  • Tanuma S, Kawashima K, Endo N (1988) Eukaryotic mono(ADP-ribosyl)transferase that ADPribosylates GTP-binding regulatory G1 protein. J Biol Chem 263:5485–5489

    Google Scholar 

  • Touchot N, Chardin P, Tavitian A (1987) Four additional members of the ras gene superfamily isolated by an oligonucleotide strategy: molecular cloning of YPT-related cDNAs from a rat brain library. Proc Natl Acad Sci USA 84:8210–8214

    Google Scholar 

  • Trahey M, McCormick F (1987) A cytoplasmic protein stimulates normal N-ras p21 GTPase, but does not affect oncogenic mutants. Science 238:542–545

    Google Scholar 

  • Tsai SC, Adamik R, Kanaho Y, Hewlett EL, Moss J (1984) Effects of guanyl nucleotides and rhodopsin on ADP-ribosylation of the inhibitory GTP-binding component of adenylate cyclase by pertussis toxin. J Biol Chem 259:15320–15323

    Google Scholar 

  • Ui M (1984) Islet-activating protein, pertussis toxin: a probe for functions of the inhibitory guanine nucleotide regulatory component of adenylate cyclase. Trends Pharmacol Sci 5:277–279

    Google Scholar 

  • Vandekerckhove J, Weber K (1979) The complete amino acid sequence of actins from bovine aorta, bovine heart, bovine fast skeletal muscle and rabbit slow skeletal muscle. Differentiation 14:123–133

    Google Scholar 

  • Vandekerckhove J, Schering B, Bärmann M, Aktories K (1987) Clostridium-perfringens iota toxin ADP-ribosylates skeletal muscle actin in Arg-177. FEBS Lett 225:48–52

    Google Scholar 

  • Vandekerckhove J, Schering B, Bärmann M, Aktories K (1988) Botulinum C2 toxin ADP-ribosylates cytoplasmic β/γ-actin in arginine 177. J Biol Chem 263:696–700

    Google Scholar 

  • Wegner A (1976) Head tail polymerization of actin. J Mol Biol 108:139–150

    Google Scholar 

  • Wegner A, Aktories K (1988) ADP-ribosylated actin caps the barbed ends of actin filaments. J Biol Chem 263:13739–13742

    Google Scholar 

  • Weigt C, Just I, Wegner A, Aktories K (1989) Nonmuscle actin ADP-ribosylated by botulinum C2 toxin caps actin filaments. FEES Lett 246:181–184

    Google Scholar 

  • Wieland T, Ulibarri I, Aktories K, Gierschik P, Jakobs KH (1990) Interaction of small G proteins with photoexcited rhodopsin. FEBS Lett (in press)

  • Yeramian P, Chardin P, Madaule P, Tavitian A (1987) Nucleotide sequence of human rho cDNA clone 12. Nucleic Acids Res 15:1869

    Google Scholar 

  • Zepeda H, Considine RV, Smith HL, Sherwin JA, Ohishi I, Simpson LL (1988) Actions of the Clostridium botulinum binary toxin on the structure and function of Y-1 adrenal cells. J Pharmacol Exp Ther 246:1183–1189

    Google Scholar 

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  1. Pharmakologisches Institut des Universitätsklinikums Essen, Hufelandstr. 55, D-4300, Essen, Germany

    Klaus Aktories

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Aktories, K. Clostridial ADP-ribosyltransferases — Modification of low molecular weight GTP-binding proteins and of actin by clostridial toxins. Med Microbiol Immunol 179, 123–136 (1990). https://doi.org/10.1007/BF00202390

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