CYTOTOXIC EFFECTS BY MICROINJECTION OF ADP RIBOSYLATED SKELETAL-MUSCLE G-ACTIN IN PTK2 CELLS IN THE ABSENCE OF CLOSTRIDIUM-PERFRINGENS IOTA-TOXIN

The ADP-ribosylating toxins Clostridium botulinum C2 toxin and C. perf ringens iota toxin, which ADP-ribosylate monomeric G-actin at Arg-177 but not the polymeric F-actin, induce depolymerization of the actin cy toskeleton in cultured cells. Since ADP-ribosylated G-actin has proper ties of a barbed-end-capping protein, we studied whether the ADP-ribos ylated actin affects the actin cytoskeleton of PtK2 cells even in the absence of ADP-ribosylating toxin. Skeletal muscle actin was ADP-ribos ylated by C. perfringens iota toxin and the toxin was removed using an anti-iota toxin antibody. Microinjection of ADP-ribosylated actin cau sed retraction of the cell body, redistribution and depolymerization o f the actin cytoskeleton in a concentration- and time-dependent manner . The finding that ADP-ribosylated actin affects per se the actin cyto skeleton explains the cytopathic effects of ADP-ribosylating toxins on microfilaments, although F-actin is not directly modified by the toxi ns.