title: Facing glycosphingolipid-Shiga toxin interaction: dire straits for endothelial cells of the human vasculature.
abstract: The two major Shiga toxin (Stx) types, Stx1 and Stx2, produced by enterohemorrhagic Escherichia coli (EHEC) in particular injure renal and cerebral microvascular endothelial cells after transfer from the human intestine into the circulation. Stxs are AB(5) toxins composed of an enzymatically active A subunit and the pentameric B subunit, which preferentially binds to the glycosphingolipid globotriaosylceramide (Gb3Cer/CD77). This review summarizes the current knowledge on Stx-caused cellular injury and the structural diversity of Stx receptors as well as the initial molecular interaction of Stxs with the human endothelium of different vascular beds. The varying lipoforms of Stx receptors and their spatial organization in lipid rafts suggest a central role in different modes of receptor-mediated endocytosis and intracellular destiny of the toxins. The design and development of tailored Stx neutralizers targeting the oligosaccharide-toxin recognition event has become a very real prospect to ameliorate or prevent life-threatening renal and neurological complications.
authors: Institute for Hygiene, University of Münster, Robert-Koch-Str. 41, 48149, Münster, Germany.
authors: Andreas
authors: A
authors: Bauwens
authors: Josefine
authors: J
authors: Betz
authors: Iris
authors: I
authors: Meisen
authors: Björn
authors: B
authors: Kemper
authors: Helge
authors: H
authors: Karch
authors: Johannes
authors: J
authors: Müthing
mesh_terms: D004705:Endocytosis; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D006028:Glycosphingolipids / Q000378:metabolism*; D006801:Humans; D021962:Membrane Microdomains / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism; D022621:Shiga Toxin / Q000378:metabolism*; D014281:Trihexosylceramides / Q000378:metabolism
chemical_list: D006028:Glycosphingolipids; D011956:Receptors, Cell Surface; D014281:Trihexosylceramides; D022621:Shiga Toxin