tailieunhanh - Báo cáo khoa học: Functionally different pools of Shiga toxin receptor, globotriaosyl ceramide, in HeLa cells

Many studies have investigated the intracellular trafficking of Shiga toxin, but very little is known about the underlying dynamics of its cellular recep-tor, the glycosphingolipid globotriaosyl ceramide. In this study, we show that globotriaosyl ceramide is required not only for Shiga toxin binding to cells, but also for its intracellular trafficking. | ỊFEBS Journal Functionally different pools of Shiga toxin receptor globotriaosyl ceramide in HeLa cells Thomas Falguieres1 Winfried Reimer1 Mohamed Amessou1 Carlos Afonso2 Claude Wolf3 Jean-Claude Tabet2 Christophe Lamaze1 and Ludger Johannes1 1 Laboratoire Trafic et Signalisation Unite Mixte de Recherche 144 Institut Curie CNRS Paris France 2 Laboratoire de Chimie Structurale Organique et Biologique Unite Mixte de Recherche 7613 Universite Pierre et Marie Curie Paris France 3 Centre Hospitalier Universitaire Saint-Antoine Unite Mixte de Recherche 538 INSEHM UMPC Universite Pierre et Marie Curie Paris France Keywords globotriaosylceramide HeLa cells membrane microdomains molecular species Shiga toxin Correspondence L. Johannes Unite Mixte de Recherche 144 Institut Curie CNRS 26 rue d Ulm 75248 Paris cedex 05 Fax 33 1 42 34 65 07 Tel 33 1 42 34 63 51 E-mail johannes@ Present address University of Geneva Science II Department of Biochemistry Geneva Switzerland Received 4 July 2006 revised 23 August 2006 accepted 27 September 2006 doi Many studies have investigated the intracellular trafficking of Shiga toxin but very little is known about the underlying dynamics of its cellular receptor the glycosphingolipid globotriaosyl ceramide. In this study we show that globotriaosyl ceramide is required not only for Shiga toxin binding to cells but also for its intracellular trafficking. Shiga toxin induces globotria-osyl ceramide recruitment to detergent-resistant membranes and subsequent internalization of the lipid. The globotriaosyl ceramide pool at the plasma membrane is then replenished from internal stores. Whereas endo-cytosis is not affected in the recovery condition retrograde transport of Shiga toxin to the Golgi apparatus and the endoplasmic reticulum is strongly inhibited. This effect is specific as cholera toxin trafficking on GM1 and protein biosynthesis are not impaired. The differential behavior of both toxins is also .