Abstract
The mode of action on actin polymerization of skeletal muscle actin ADP-ribosylated on arginine 177 by perfringens iota toxin was investigated. ADP-ribosylated actin decreased the rate of nucleated actin polymerization at substoichiometric ratios of ADP-ribosylated actin to monomeric actin. ADP-ribosylated actin did not tend to copolymerize with actin. Actin filaments were depolymerized by the addition of ADP-ribosylated actin. The maximal monomer concentration reached by addition of ADP-ribosylated actin was similar to the critical concentration of the pointed ends of actin filaments. ADP-ribosylated actin had no effect on the rate of polymerization of gelsolin-capped actin filaments which polymerize at the pointed ends. The results suggest that ADP-ribosylated actin acts as a capping protein which binds to the barbed ends of actin filaments to inhibit polymerization. Based on an analysis of the depolymerizing effect of ADP-ribosylated actin, the equilibrium constant for binding of ADP-ribosylated actin to the barbed ends of actin filaments was determined to be about 10(8) M-1. As actin is ADP-ribosylated by perfringens iota toxin and by botulinum C2 toxin, it appears that conversion of actin into a capping protein by ADP-ribosylation is a pathophysiological reaction catalyzed by bacterial toxins which ultimately leads to inhibition of actin assembly.
Highlights
The mode of action on actin polymerization of skeletal muscle actin ADP-ribosylated on arginine 177 by perfringens iota toxinwasinvestigated
ADP-ribosylated actin concentrations which were substoichiometric compared with monomeric actin were sufficient to retard actin polymerization significantly;0.1 pM ADP-ribosylated actin decreasedthe rate of nucleated polymerization of 1p M actin 2-3-fold (Fig. 1)
The critical monomer concentration of the pointed ends of gelsolin-capped filaments is about 0.7 FM. This value corresponds approximately to themaximal monomer concentration reached by addition of ADP-ribosylated actin
Summary
From the Slnstitute of Physiological Chemistry, Ruhr-University Bochum,0-4630 Bochum, Federal Republicof Germany and the llRudolf-BuchheimInstitute of Pharmacology, Frankfurter Strasse 107,0-6300 Giessen, Federal Republic of Germany. The results suggest that ADP-ribosylated actin acts as a capping protein which binds to the barbed ends of actin filaments to inhibit polymerization. As actin is ADPribosylated by perfringens iota toxin and by botulinum C2 toxin,it appears that conversion of actin into a capping protein by ADP-ribosylation is a pathophysiological reaction catalyzed by bacterial toxins which leads to inhibition of actin assembly. Bacterial ADP-ribosyltransferases such as perfringens iota and botulinum C2 toxin ADP-ribosylate actin on arginine 177. (9, lo), thereby largely reducing the ability of actin to polymerize [5, 7, 8] Both clostridial toxins consist of a low and a high molecular mass component [11,12]. Actin is lacking, we investigated the mechanism of the action of actin ADP-ribosylated by perfringens iota toxin
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
