Uptake and Trafficking of Protein Toxins

Description

This volume focuses on the transport of medically relevant bacterial protein toxins into mammalian cells, and on novel pharmacological strategies to inhibit toxin uptake. The first chapters review our current understanding of the cell-surface receptors and cellular transport processes of Clostridium botulinum neurotoxins, Clostridium botulinum C3 toxin, Clostridium difficile toxins, binary clostridial enterotoxins, anthrax toxins and diphtheria toxin. In brief, specific binding/transport (B) subunits deliver the enzyme (A) subunits into the cytosol, where the latter modify their substrates, producing cytotoxic effects and the characteristic toxin-associated diseases. Key mechanisms for the transport of the A subunits from endosomes into the cytosol and the role of trans-membrane pores formed by the B subunits and host cell chaperones for this process are reviewed. The book’s closing chapters focus on compounds which inhibit the transport of the A subunits from endosomes into the cytosol and therefore might lead to novel therapeutic strategies for toxin-associated diseases. These substances include pharmacological inhibitors of the host cell chaperones involved, as well as multivalent and heterocyclic molecules that specifically block the toxins’ translocation channels. This volume offers an up-to-date resource for scientists. Front Matter ....Pages i-vii Two Feet on the Membrane: Uptake of Clostridial Neurotoxins (Andreas Rummel)....Pages 1-37 Uptake of Clostridial Neurotoxins into Cells and Dissemination (Chloé Connan, Michel R. Popoff)....Pages 39-78 Receptors and Binding Structures for Clostridium difficile Toxins A and B (Ralf Gerhard)....Pages 79-96 Cell Entry of C3 Exoenzyme from Clostridium botulinum (Astrid Rohrbeck, Ingo Just)....Pages 97-118 Receptor-Binding and Uptake of Binary Actin-ADP-Ribosylating Toxins (Panagiotis Papatheodorou, Klaus Aktories)....Pages 119-133 Clostridial Binary Toxins: Basic Understandings that Include Cell Surface Binding and an Internal “Coup de Grâce” (Bradley G. Stiles)....Pages 135-162 Host Cell Chaperones Hsp70/Hsp90 and Peptidyl-Prolyl Cis/Trans Isomerases Are Required for the Membrane Translocation of Bacterial ADP-Ribosylating Toxins (Katharina Ernst, Leonie Schnell, Holger Barth)....Pages 163-198 Multivalent Inhibitors of Channel-Forming Bacterial Toxins (Goli Yamini, Ekaterina M. Nestorovich)....Pages 199-227 Toxin Transport by A-B Type of Toxins in Eukaryotic Target Cells and Its Inhibition by Positively Charged Heterocyclic Molecules (Roland Benz, Holger Barth)....Pages 229-256