The Open Toxinology Journal

2010, 3 : 13-18
Published online 2010 March 10. DOI: 10.2174/1875414701003010013
Publisher ID: TOTNJ-3-13

Glucosylation of Rho/Ras Proteins by Lethal Toxin – Implications of Actin Re-Organization and Apoptosis in -Associated Disease

Harald Genth , Florian Schulz and Ingo Just
this author at the Institute of Toxicology, Hannover Medical School, D-30623 Hannover, Germany;

ABSTRACT

Clostridium sordellii causes disease in livestock and life-threatening illnesses in humans. Pathogenic C. sordellii strains produce up to seven virulence factors, including lethal toxin (TcsL), hemorrhagic toxin, a hemolysin, a DNAse, a collagenase, and a lysolecithinase cell. TcsL exhibits an A-B toxin-like structure and enters its target cells by receptor-mediated endocytosis. Inside the, TcsL mono-glucosylates low molecular weight GTP-binding proteins of the Ras and Rho families. This article reviews recent progress for (i) re-enforcing (H/K/N)Ras glucosylation and subsequent inhibition of the phosphoinositide 3-kinase (PI3K) / Akt survival signalling pathway as the cause of TcsL-induced apoptotic cell death, and (ii) showing the critical nature of Rac1 glucosylation in the loss of epithelial and endothelial barrier function. Finally, the detection of TcsL-induced glucosylation of Rac1 and (H/K/N)Ras using glucosylationsensitive antibodies is presented as a new method to track TcsL activity.

Keywords:

MyonecrosisA, Phagocytosisacid, Mono-glucosylation, (H/K/N)Ras, Rac.