Globotriaosyl ceramide receptor function - where membrane structure and pathology intersect.
The glycosphingolipid globotriaosyl ceramide, (Galalpha1-4Galss1-4 glucosyl ceramide-Gb(3)) also known as CD77 and the P(k) blood group antigen, is bound by both verotoxins and by the HIV adhesin, gp120. Gb(3) plays an important receptor role in VT induced hemolytic uremic syndrome (HUS) and HIV infection. The organization of glycolipids, including Gb(3), into lipid rafts is central to both pathologies. The fatty acid heterogeneity within the Gb(3) lipid moiety plays a central role in assembly within such ordered domains. Differential binding of verotoxins and gp120 to such Gb(3) isoforms in model and cell membranes indicates a significant role in the eventual pathogenic outcome. HUS may provide the first example whereby membrane Gb(3) organization provides a predictor for tissue selective in vivo pathology.
Lingwood
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CA
Research Institute, Division of Molecular Structure and Function, The Hospital for Sick Children, Toronto, Ontario, Canada. cling@sickkids.ca
Binnington
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B
Manis
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A
Branch
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DR
D000818:Animals; D021961:Cell Membrane Structures / Q000473:pathology / Q000502:physiology*; D006028:Glycosphingolipids / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000378:metabolism / Q000502:physiology; D015658:HIV Infections / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology; D022603:Shiga Toxins / Q000378:metabolism; D014281:Trihexosylceramides / Q000378:metabolism / Q000502:physiology*
D006028:Glycosphingolipids; D015699:HIV Envelope Protein gp120; D011956:Receptors, Cell Surface; D022603:Shiga Toxins; D014281:Trihexosylceramides; C514793:gp120 protein, Human immunodeficiency virus 1; C018549:globotriaosylceramide