Actin Clostridium botulinum

The binary Clostridium botulinum toxin C2 blocks the function of actin filaments similarly to cytochalasin D (92). Treatment is for one to four hours in concentrations of 50ng/100ng or 100ng/200ng prior to adding liposomes. 

Clostridium botulinum C2 toxin The prototype of a binary actin-ADP-ribosylating toxin 155... 

C2 Clostridium botulinum Binary Actin Depolymerization of F-actin (see text)... 

OlARDIN P, BOQUET P, MADAULE P, POPOFF MR, RUBIN EJ, GlLL DM. The mammalian G protein rhoC is ADP ribosylated by Clostridium botulinum exoenqnne C3 and affects actin microfilaments in Vero cells. EMBOJ8 1087-1092,1988. 

Chardin, P, Boquet, P, Moduale, P et al. (1989) The mammalian protein rhoC is ADP-ribosylated by Clostridium botulinum exoenzyme C3 and affects actin microfilaments in vero cells. In EMBOJ. 8 1087—92. 

Actin-ADP-ribosylating Toxins Cytotoxic Mechanisms of Clostridium botulinum C2 Toxin and Clostridium perfringens lota Toxin... 

Grolig F, Just I, Aktories K (1996) ADP-ribosylation of actin from the green alga Chara corollino by Clostridium botulinum C2 toxin and Clostridium perfringens iota toxin. In Protoplasma in press... 

Just I, Geipel U, Wegner A et al. (1990) De-ADP-ribosylation of actin by Clostridium perfringens iota-toxin and Clostridium botulinum C2 toxin. In Eur. J. Biochem. 192 ... 

Just I, Wille M, Chaponnier C et al. (1993b) Gelsolin-actin complex is target for ADP-ribosylation by Clostridium botulinum C2 toxin in intact human neutrophils. In Eur. J. Pharmacol. Mol. Pharmacol. 246 293-7 Kiefer A, Lerner M, Sehr P et al. (1996) Depolymerization of F-actin by microinjection of ADP-ribosylated skeletal muscle G-actin in PtK2 cells in the absence of the ADP-ribosylating toxin. In A/ted. Microbiol. Immunol. 184 175-80 Mauss S, Chaponnier C, Just I et al. (1990) ADP-ribosylation of actin isoforms by Clostridium botulinum C2 toxin and Clostridium perfringens iota toxin. In Eur. J. Biochem. 194 237-41... 

Weigt C, Just I, Wegner A et al. (1989) Nonmuscle actin ADP-ribosylated by botuli-num C2 toxin cops actin filaments. In FEBS Lett. 246 181 -4 Wiegers W, Just I, Moller H et al. (1991) Alteration of the cytoskeleton of mammalian cells cultured in vitro by Clostridium botulinum C2 toxin and C3 ADP-ribosyltransferase. In Eur. J. Cell Biol. 54 237-45 Wille M, Just I, Wegner A et al. (1992) ADP-ribosylation of the gelsolin-actin complex by clostridial toxins. In J. Biol. Chem. 267 50-5... 

Li G, Rungger-Brandle E, Just I, etal. (1994) Effect of disruption of actin filaments by Clostridium botulinum C2 toxin on insulin secretion in HIT-T15 cells and pancreatic islets. In Molecular Biology of the Cell. 5 1199—213... 

Reuner KH, Schlegel K, Just I, et al. (1991) Autoregulatory control of actin synthesis in cultured rat hepatocytes. In FEBS Letters. 286 100-4 Schmid A, Benz R, Just I, et al. (1994) Interaction of Olostridium botulinum 02 toxin with lipid bilayer membranes. Formation of cation-selective channels and inhibition of channel function by chloroquine. In J Biol Chem. 269 16706-11 Simpson LL (1982) A comparison of the pharmacological properties of Clostridium botulinum type 01 and 02 toxins. In J Pharmacol Exp Then 223 695-701 Simpson LL (1989a) Botulinum Neurotoxin andTetanus Toxin, pp 1 -422, San Diego Academic Press... 

Probing the Actin Cytoskeleton by Clostridium botulinum C2 Toxin and Clostridium pedringens lota Toxin 137... 

It is therefore necessary to distinguish between cellular effects caused merely by depolymerization of the actin filaments and effects caused by inactivation of the Rho GTPases which are independent of the actin system. To this end, it is very helpful to compare effects of toxin B with those of Clostridium botulinum C2 toxin. C2 toxin directly acts... 

Inactivation of Rho with Clostridium botulinum C3 ADP-ribosyl-transferase (C3 exoenzyme, which specifically ADP-ribosylates and inactivates Rho) inhibits neutrophil chemotaxis to N-formyl peptides [369, 443] without inhibiting the initiation of actin polymerization [94]. Microscopic examination of these cells reveals that they are unaffected in their abilities to polarize and extend pseudopodia, rather C3 exoenzyme inhibition of migration is associated with inhibition of rear release. 

So far eight different botulinum toxins (A, B, Cl, C2, D, E, F, G) have been described which are produced by various strains of Clostridium botulinum (1). Whereas seven of the botulinum toxins are neurotoxins and block the release at the cholinergic synapses, botulinum C2 toxin is not neurotoxic and acts on various non-neuronal tissues (1-3). It has been shown that component I of the binary botulinum C2 toxin possesses ADP-ribosyltransferase activity (4) on the eukaryotic substrate non-muscle actin (5). Here we describe another ADP-ribosyltransferase which is produced by certain strains of Clostridium botulinum type C. In order to distinguish the novel ADP-ribosyltransferase from botulinum neurotoxin Cl and botulinum C2 toxin we termed this enzyme C3. 

Another subfamily of ADP-iibosylating toxins modifies G-actin (at Argl77), thereby inhibiting actin polymerization. Members of this family are, for example, C. botulinum C2 toxin and Clostridium perfringens iota toxin. These toxins are binary in structure. They consist of an enzyme component and a separate binding component, which is structurally related to the binding component of anthrax toxin [3]. 

Pollard TD, Almo S, Quirk S etal. (1994) Structure of actin binding proteins Insights about function at atomic resolution. In Annu. Rev. Cell Biol. 10 207-49 Popoff MR, Rubin EJ, Gill DM et al. (1988) Actin-specific ADP-ribosyltransferase produced by a Clostridium difficile strain. In Infect. Immun. 56 2299-306 Popoff MR, Boquet P (1988) Clostridium spiroforme toxin is a binary toxin which ADP-ribosylates cellular actin. In Biochem. Biophys. Res. Commun. 152 1361—8 Reuner KH, Presek P, Boschek CB et al. (1987) Botulinum C2 toxin ADP-ribosylates actin and disorganizes the microfilament network in intact cells. In Eur. J. Cell Biol. 43 134-40... 

In the past decade, toxins produced by various species of Clostridium were reported to disrupt the ACTSK by ADP-ribosylation of either actin, as does the C2-toxin from C. botulinum (Aktories et al., 1986 Reuner et al., 1987), or the small GTPase Rho, as does exoenzyme C3 from the same bacterium (Aktories et al., 1987 Chardin et al., 1989). However, neither of the C. difficile toxins was found to have any ADP-ribosyltransferase activity (Florin and Thelestam, 1991 Just et al., 1994b Popoff eta/., 1988). 

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