Endocytosis and toxicity of clostridial binary toxins depend on a clathrin‐independent pathway regulated by Rho‐GDI |
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| Authors: | Maryse Gibert Marie‐Noëlle Monier Richard Ruez Martha L Hale Bradley G Stiles Alexandre Benmerah Ludger Johannes Michel R Popoff |
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| Institution: | 1. Institut Pasteur, Bactéries anaérobies et Toxines, 25 rue du Dr Roux, 75724 Paris Cedex 15, France;2. CNRS UMR144, 75248 Paris Cedex 05, France;3. Institut Curie, Centre de Recherche, Laboratoire Trafic, Signalisation et Ciblage Intracellulaires, 26 rue d'Ulm, 75248 Paris Cedex 05, France;4. Toxinology Division, Department of Immunology and Molecular Biology, US Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702‐5011, USA;5. Protéines Virales et Trafics Intracellulaires, Institut Cochin, Paris, France |
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| Abstract: | Clostridial binary toxins, such as Clostridium perfringens Iota and Clostridium botulinum C2, are composed of a binding protein (Ib and C2II respectively) that recognizes distinct membrane receptors and mediates internalization of a catalytic protein (Ia and C2‐I respectively) with ADP‐ribosyltransferase activity that disrupts the actin cytoskeleton. We show here that the endocytic pathway followed by these toxins is independent of clathrin but requires the activity of dynamin and is regulated by Rho‐GDI. This endocytic pathway is similar to a recently characterized clathrin‐independent pathway followed by the interleukin‐2 (IL2) receptor. We found indeed that Ib and C2II colocalized intracellularly with the IL2 receptor but not the transferrin receptor after different times of endocytosis. Accordingly, the intracellular effects of Iota and C2 on the cytoskeleton were inhibited by inactivation of dynamin or by Rho‐GDI whereas inhibitors of clathrin‐dependent endocytosis had no protective effect. |
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