ADP-ribosylated actin caps the barbed ends of actin filaments.
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.
D036002:ADP Ribose Transferases; D000199:Actins / Q000378:metabolism*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D003016:Clostridium perfringens; D018260:Gelsolin; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D008840:Microfilament Proteins / Q000378:metabolism; D009132:Muscles / Q000032:analysis; D011108:Polymers; D011817:Rabbits
D000199:Actins; D001427:Bacterial Toxins; D002135:Calcium-Binding Proteins; D018260:Gelsolin; D046911:Macromolecular Substances; D008840:Microfilament Proteins; D011108:Polymers; C050737:iota toxin, Clostridium perfringens; D000246:Adenosine Diphosphate Ribose; D036002:ADP Ribose Transferases