title: Endocytosis and toxicity of clostridial binary toxins depend on a clathrin-independent pathway regulated by Rho-GDI.
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.
authors.affiliation: Institut Pasteur, Bactéries anaérobies et Toxines, 25 rue du Dr Roux, 75724 Paris Cedex 15, France.
authors.forename: Maryse
authors.initials: M
authors.lastname: Gibert
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Monier
authors.forename: Richard
authors.initials: R
authors.lastname: Ruez
authors.forename: Martha L
authors.initials: ML
authors.lastname: Hale
authors.forename: Bradley G
authors.initials: BG
authors.lastname: Stiles
authors.forename: Alexandre
authors.initials: A
authors.lastname: Benmerah
authors.forename: Ludger
authors.initials: L
authors.lastname: Johannes
authors.forename: Christophe
authors.initials: C
authors.lastname: Lamaze
authors.forename: Michel R
authors.initials: MR
authors.lastname: Popoff
mesh_terms: D036002:ADP Ribose Transferases; D000818:Animals; D001427:Bacterial Toxins; D001905:Botulinum Toxins / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D002966:Clathrin / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism; D004705:Endocytosis; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D014709:Vero Cells; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
chemical_list: D001427:Bacterial Toxins; D002966:Clathrin; D020730:Guanine Nucleotide Dissociation Inhibitors; C050737:iota toxin, Clostridium perfringens; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors; D036002:ADP Ribose Transferases; D001905:Botulinum Toxins; D034281:Dynamins; C096324:botulinum toxin type C