The low molecular mass GTP-binding protein Rho is affected by toxin A from Clostridium difficile.
Open Access
- 1 March 1995
- journal article
- research article
- Published by American Society for Clinical Investigation in Journal of Clinical Investigation
- Vol. 95 (3) , 1026-1031
- https://doi.org/10.1172/jci117747
Abstract
Enterotoxin A is one of the major virulence factors of Clostridium difficile, and the causative agent of antibiotic-associated pseudomembranous colitis. In cell culture (NIH-3T3, rat basophilic leukemia cells) toxin A inhibits Clostridium botulinum ADP-ribosyltransferase C3 (C3)-catalyzed ADP-ribosylation of the low molecular mass GTP-binding Rho proteins. Rho participates in the regulation of the microfilament cytoskeleton. Decrease in ADP-ribosylation of Rho occurs in a time- and concentration-dependent manner and precedes the toxin A-induced destruction of the actin cytoskeleton. Action of toxin A is not due to proteolytical degradation of Rho or to an inherent ADP-ribosyltransferase activity of toxin A. Toxin A-induced decrease in ADP-ribosylation is observed also in cell lysates and with recombinant RhoA protein. A heat stable low molecular mass cytosolic factor is essential for the toxin effect on Rho. Thus, the enterotoxin (toxin A) resembles the effects of the C. difficile cytotoxin (toxin B) on Rho proteins (Just, I., G. Fritz, K. Aktories, M. Giry, M. R. Popoff, P. Boquet, S. Hegenbath, and C. Von Eichel-Streiber. 1994. J. Biol. Chem. 269:10706-10712). The data indicate that despite different in vivo effects, toxin A and toxin B act on the same cellular target protein Rho to elicit their toxic effects.Keywords
This publication has 42 references indexed in Scilit:
- The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factorsCell, 1992
- ADP-ribosylation of small GTP-binding proteins by Bacillus cereusBiochemical and Biophysical Research Communications, 1992
- ADP-ribosylation of a small size GTP-binding protein in bovine neutrophils by the C3 exoenzyme of Clostridium botulinum and effect on the cell motilityBiochemical and Biophysical Research Communications, 1991
- Partial purification and characterization of GDP dissociation stimulator (GDS) for the rho proteins from bovine brain cytosolBiochemical and Biophysical Research Communications, 1990
- Clostridium difficile toxin A carries a C-terminal repetitive structure homologous to the carbohydrate binding region of streptococcal glycosyltransferasesGene, 1990
- Clostridium difficile toxin B induces reorganization of actin, vinculin, and talin in cultured cellsExperimental Cell Research, 1988
- Effects of cytochalasin and phalloidin on actin.The Journal of cell biology, 1987
- Rapid death of infant rhesus monkeys injected with Clostridium difficile toxins A and B: Physiologic and pathologic basisThe Journal of Pediatrics, 1984
- Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.Proceedings of the National Academy of Sciences, 1979
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970