Differential requirement for the translocation of clostridial binary toxins: Iota toxin requires a membrane potential gradient

Gibert, Maryse; Marvaud, Jean Christophe; Pereira, Yannick; Hale, Martha L.; Stiles, Bradley G.; Boquet, Patrice; Lamaze, Christophe; Popoff, Michel R.

doi:10.1016/j.febslet.2007.02.041

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Volume 581, Issue 7 , Pages 1287-1296, 3 April 2007

Differential requirement for the translocation of clostridial binary toxins: Iota toxin requires a membrane potential gradient

Edited by Pascale Cossart

Maryse Gibert
- Bactéries Anaérobies et Toxines, Institut Pasteur, Paris, France
Jean Christophe Marvaud
- Bactéries Anaérobies et Toxines, Institut Pasteur, Paris, France
Yannick Pereira
- Bactéries Anaérobies et Toxines, Institut Pasteur, Paris, France
Martha L. Hale
- Toxinology Division, Department of Immunology and Molecular Biology, US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702-5011, USA
Bradley G. Stiles
- Toxinology Division, Department of Immunology and Molecular Biology, US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702-5011, USA
Patrice Boquet
- INSERM U452, Faculté de Médecine, Nice, France
Christophe Lamaze
- Laboratoire Trafic et Signalisation, UMR144 Curie/CNRS, Institut Curie, 26 Rue d’Ulm, Paris, France
Michel R. Popoff
- Bactéries Anaérobies et Toxines, Institut Pasteur, Paris, France
- Corresponding author. Fax: +33 1 40 61 31 23.

Received 15 September 2006; received in revised form 14 December 2006; accepted 13 February 2007. published online 01 March 2007.

Abstract

Clostridial binary toxins, such as Clostridium perfringens Iota and Clostridium botulinum C2, are composed of a binding protein (Ib and C2-II, respectively) that recognizes distinct membrane receptors and mediates internalization of a catalytic protein (Ia and C2-I, respectively) with ADP-ribosyltransferase activity that depolymerizes the actin cytoskeleton. After internalization, it was found that C2 and Iota toxins were not routed to the Golgi apparatus and exhibited differential sensitivity to inhibitors of endosome acidification. While the C2-I component of C2 toxin was translocated into the cytosol from early endosomes, translocation of the Ia component of Iota toxin occurred between early and late endosomes, was dependent on more acidic conditions, and uniquely required a membrane potential gradient.

Keywords: Iota toxin, C2 toxin, Membrane potential, Translocation, Endocytosis, Clostridium