| dc.description |
ADP-ribosylation of regulatory proteins is an important pathological mechanism by which various bacterial toxins affect eukary-otic cell functions. While diphtheria toxin catalyses the ADP-ribosylation of elongation factor 2, which results in inhibition of protein synthesis, cholera toxin and pertussis toxin ADP-ribosylate Ns and Ni respectively, the GTP-binding regulatory components of the adenylate cyclase system, thereby modulating the bidirectional hormonal regulation of the adenylate cyclase<sup>1,2</sup>Botulinum C2 toxin is another toxin which has been reported to possess ADP-ribosyltransferase activity<sup>3</sup>. This extremely toxic agent is produced by certain strains of Clostridium botulinum<sup>4</sup> and induces hypotension<sup>5</sup>, an increase in intestinal secretion<sup>6</sup> vascular permeability<sup>7</sup> and haemorrhaging in the lungs<sup>5</sup>. In contrast to botulinum neurotoxins, the botulinum C2 toxin apparently lacks any neurotoxic effects<sup>5</sup>. Here we report that botulinum C2 toxin ADP-ribosylates a protein of relative molecular mass 43,000 (43K) in intact cells and in cell-free preparations. We present evidence that the 43K protein substrate is actin, which is apparently mono-AD P-ribosylated by the toxin. Botulinum C2 toxin also ADP-ribosylated purified liver G-actin, whereas liver F-actin was only poorly ADP-ribosylated and skeletal muscle actin was not ADP-ribosylated in either its G form or its F form. ADP-ribosylation of liver G-actin by botulinum C2 toxin resulted in a drastic reduction in viscosity of actin polymerized in vitro. |
