The uptake machinery of clostridial actin ADP-ribosylating toxins--a cell delivery system for fusion proteins and polypeptide drugs.
Several bacterial protein toxins, including Clostridium botulinum C2 toxin, Clostridum perfringens iota toxin, Clostridium difficile ADP-ribosyltransferase, and the Bacillus-produced vegetative insecticidal proteins, target the cytoskeleton by ADP-ribosylation of actin. All these toxins are binary in structure and consist of an enzyme component, possessing ADP-ribosyltransferase activity and a separated binding and translocation component, which is involved in the delivery of the enzyme component into the cell. The toxins are not only important virulence factors but also cell biological tools to study the function of the actin cytoskeleton. Moreover, the binary toxins turned out to be effective transporter systems for the delivery of specific fusion toxins (e.g., Rho-ADP-ribosylating C3 exoenzyme) into cells. The present review describes the biological functions of the toxins, focuses on recent studies on the uptake and delivery mechanism and discusses the usage as a drug delivery system.
Barth
Holger
H
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert-Ludwigs-Universität Freiburg, Otto-Krayer-Haus, Albertstrasse 25, 79104 Freiburg; Germany. holger.barth@pharmakol.uni-freiburg.de
Blöcker
Dagmar
D
Aktories
Klaus
K
D036002:ADP Ribose Transferases / Q000378:metabolism*; D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D003013:Clostridium / Q000378:metabolism; D006801:Humans; D010455:Peptides / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism*
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D036002:ADP Ribose Transferases; C410164:actin-specific ADP-ribosyltransferase, Clostridium; D020727:ADP-Ribosylation Factors