Microfilaments toxin

Allingham JS, Zampella A, D Auria MV et al (2005) Structures of microfilament destabilizing toxins bound to actin provide insight into toxin design and activity. Proc Natl Acad Sci USA 102 14527-14532... 

Colchicine is allelochemical from Colchicium genera, which binds the tubulin and prevents the mitosis (Fig. 2) Cytochalasin B, cell permeable fungal toxin from Helminthosporium dematiodeum, which inhibits cell division by blocking the active polymerization and formation of contractile actomyosin microfilaments, inhibit the germination of microspores (Roshchina, 2005a). Therefore, one mechanism of action of some allelochemicals from plants and... 

Synaptobrevins (VAMPs) Synaptogyrin Synaptophysins PKA but diverge C-terminally. Synapsins Ia/b contain C-terminal phosphorylation sites for CaMKII and CDK 5. Interact with microfilaments, neurofilaments, microtubules, SH3 domains, calmodulin and annexin VI in vitro. Small-membrane proteins that are cleaved by tetanus toxin and by botulinum toxins B, D, F and G. Polytopic membrane protein that is tyrosine-phosphorylated. Function unknown. Polytopic membrane proteins, including synaptoporin, that are tyrosine-phosphorylated and bind to synaptobrevins. May regulate SNARE function... 

Spector I, Shochet N, Kashman Y, Groweiss A, Latrunculins Novel marine toxins that disrupt microfilament organization in cultured cells, Science... 

The natural toxin microcytin damages microfilaments by acting as a protein phosphatase inhibitor, thus increasing the phosphorylation of the proteins. 

Aullo P, Giry M, Olsnes S et al. (1993) A chimeric toxin to study the role of the 21 kDa GTP binding protein rho in the control of actin microfilament assembly. In EMBO J. 12 921 -31... 

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... 

Considine RV, Simpson LL, Sherwin JR (1992) Botulinum C2 toxin and steroid production in adrenal Y-1 cells The role of microfilaments in the toxin-induced increase in steroid release. In J Pharmacol Exp Then 260 859-64... 

Mauss S, Koch G, Kreye VA, et al. (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. In Noun-Schmiedebergs Archiv Pharmacol. 340 345-51 Melamed I, Downey GP, Aktories K, et al. (1991) Microfilament assembly is required for antigen-receptor-mediated activation of human B lymphocytes. In J Immunol. 147 1139-46... 

Reuner KH, Presek P, Boschek OB, etal. (1987) Botulinum 02 toxin ADP-ribosylates actin and disorganizes the microfilament network in intact cells. In European Journal of Cell Biology. 43 134-40... 

C. botulinum C2 toxin and C perfringens iota toxin belong to the family of actin-ADP-ribosylating toxins that transfer ADP-ribose from NAD to arginine-177 of actin. This modification results in inhibition of actin polymerization, leading to depolymerization of the microfilament network. Origin, structure, molecular mechanisms and general aspects of the use of this family of toxins is described in chapter 8, 9 and 10. 

Although the toxin s effects on the microfilament system are easily visualized by fluorescence microscopy, it may be important to determine the changes in the ratio of cellular F- and G-actin quantitatively. Because G-actin dissolves in Triton X-100, whereas F-actin (or at least a major fraction of F-actin) does not, fractionation by detergent solubility can be used to study changes in the G- and F-actin content of cells. A different approach is the determination of G-actin content by the DNAse inhibition assay according to Blikstad (Blikstad et al., 1978). The action of DNAse in cleaving DNA is inhibited by monomeric G-actin but not by F-actin. Thus, the extent of inhibition of DNAse is proportional to the concentration of G-actin in cell lysates. 

Shoshan MC, Aman P, Skog S, etal. (1990) Microfilament-disrupting Clostridium difficile toxin B causes multinucleation of transformed cells but does not block capping of membrane Ig. In Eur. J. Cell Biol. S3 357—363. 

The use of bacterial toxins as molecular probes will continue to provide valuable information on the functions of their various substrates. In addition, studies on endogenous cellular mono(ADP-ribosyl) transferases look set to expand. New substrates will be identified and the biochemical consequences of the different modifications will reveal the roles played by mono(ADP-ribosylation) reactions in different cell compartments. For example, the case of cytoskeletal actin has been discussed (see Figure 8). Work in Mandel s laboratory (Mandel, 1992) has revealed that other cytoskeletal proteins are also substrates for endogenous ADP-ribosyl transferase, including components of the microfilaments (tubulin, intermediate filaments, and the neurofilament proteins L, M, and H). 

Bubb, M. R., Spector, I., Bershadsky, A. D., and Kom, E. D. (1995). Swinholide A is a microfilament disrupting marine toxin that stabilizes actin dimers and severs actin filaments. J. Biol. Chem. 270, 3463-3466. 

Hedin U, Bottger BA, Forsberg E, Johansson S, Thyberg J (1988) Diverse effects of fibronectin and laminin on phenotypic properties of cultured arterial smooth muscle cells. J Cell Biol 107 307-319. Ronnov-Jessen L, Petersen OW (1996) ADP-ribosylation of actins in fibroblasts and myofibroblasts by botulinum C2 toxin influence on microfilament morphology and migratory behavior. Electrophoresis 17 1776-1780. 

Spector, L, N.R. Shochet, Y. Kashman, and A. Groweiss Latrunculins Novel Marine Toxins That Disrupt Microfilament Organization in Cultured Cells. Science 219, 493 (1983). 

Spector, I., Shochet, N.R., Kashman, Y, and Groweiss, A. (1983) Latrunculins novel marine toxins that disrupt microfilament organisation in cultured cells. Science, 214,493-495. 

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