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. perfringens iota toxin, which ADP-ribosylate monomeric G-actin at Arg-177 but not the polymeric F-actin, induce depolymerization of the actin cytoskeleton in cultured cells. Since ADP-ribosylated G-actin has properties of a barbed-end-capping protein, we studied whether the ADP-ribosylated actin affects the actin cytoskeleton of PtK2 cells even in the absence of ADP-ribosylating toxin. Skeletal muscle actin was ADP-ribosylated by C. perfringens iota toxin and the toxin was removed using an anti-iota toxin antibody. Microinjection of ADP-ribosylated actin caused retraction of the cell body, redistribution and depolymerization of the actin cytoskeleton in a concentration- and time-dependent manner. The finding that ADP-ribosylated actin affects per se the actin cytoskeleton explains the cytopathic effects of ADP-ribosylating toxins on microfilaments, although F-actin is not directly modified by the toxins.
Kiefer
G
G
Institut für Pharmakologie und Toxikologie, Universität des Saarlandes, Homburg-Saar, Germany.
Lerner
M
M
Sehr
P
P
Just
I
I
Aktories
K
K
D036002:ADP Ribose Transferases; D000199:Actins / Q000633:toxicity*; D000244:Adenosine Diphosphate / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D001427:Bacterial Toxins / Q000633:toxicity*; D001905:Botulinum Toxins / Q000633:toxicity; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects; D003603:Cytotoxins / Q000633:toxicity*; D008845:Microinjections
C042634:ADP-G-actin; D000199:Actins; D001427:Bacterial Toxins; D003603:Cytotoxins; C050737:iota toxin, Clostridium perfringens; D000244:Adenosine Diphosphate; D036002:ADP Ribose Transferases; D001905:Botulinum Toxins; C096324:botulinum toxin type C