Involvement of Ras-related Rho proteins in the mechanisms of action of Clostridium difficile toxin A and toxin B.
AUTOR(ES)
Dillon, S T
RESUMO
Toxins A and B of Clostridium difficile are responsible for pseudomembranous colitis, a disease that afflicts a substantial number of hospitalized patients treated with antibiotics. A major effect of these proteins is the disruption of the actin cytoskeleton. Recently, I. Just, G. Fritz, K. Aktories, M. Giry, M. R. Popoff, P. Boquet, S. Hegenbarth, and C. von Eichel-Streiber (J. Biol. Chem. 269:10706-10712, 1994) implicated Rho proteins as cellular targets of C. difficile toxin B, since pretreatment of cells or purified Rho with toxin prevented subsequent ADP-ribosylation of Rho by exoenzyme C3. Moreover, they showed that overexpression of Rho proteins in cells suppressed cell rounding normally associated with exposure of cells to C. difficile toxin B. Here we expand these findings by showing directly that Rho proteins are covalently modified by both C. difficile toxins A and B. In addition, we demonstrate that the stability of toxin-modified Rho in NIH 3T3 cells is dramatically reduced. Finally, we show that C. difficile toxins A and B do not have similar effects on the closely related Rac and CDC42 GTP-binding proteins.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=173169Documentos Relacionados
- Ras-related GTPases and the cytoskeleton.
- Molecular cloning and characterization of rho, a ras-related small GTP-binding protein from the garden pea.
- RAP2B: a RAS-related GTP-binding protein from platelets.
- Biochemical properties of the ras-related YPT protein in yeast: a mutational analysis.
- Nucleotide sequence of a human cDNA encoding a ras-related protein (rap1B).