Uncommon membrane distribution of Shiga toxin glycosphingolipid receptors in toxin-sensitive human glomerular microvascular endothelial cells
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Josefine Betz
Abstract
Membrane microdomain association of the glycosphingolipids (GSLs) globotriaosylceramide (Gb3Cer) and globotetraosylceramide (Gb4Cer), the highly and less effective receptors, respectively, for Shiga toxins (Stxs), is assumed as a functional requirement for Stx-mediated cytotoxicity. In a previous study, we demonstrated predominant localization of Stx receptors in cholesterol-enriched membrane microdomains of moderately Stx-sensitive human brain microvascular endothelial cells (HBMECs) by means of detergent-resistant membranes (DRMs). Here we report a different preferential distribution of Stx receptors in non-DRM fractions of human glomerular microvascular endothelial cells (GMVECs), the major targets of Stxs in the human kidney. Full structural characterization of Stx receptors using electrospray ionization (ESI) mass spectrometry revealed Gb3Cer and Gb4Cer lipoforms with ceramide moieties mainly composed of C24:0/C24:1 or C16:0 fatty acid and sphingosine (d18:1) in GMVECs comparable to those previously found in HBMECs. Thin-layer chromatography immunostaining demonstrated an approximately 2-fold higher content of Gb3Cer and a 1.4-fold higher content of Gb4Cer in GMVECs than in HBMECs. However, this does not explain the remarkable higher cytotoxic action of Stx1 and Stx2 toward GMVECs as compared with HBMECs. Our finding opens new questions on the microdomain association of Stx receptors and the functional role of GSLs in the membrane assembly of GMVECs.
©2012 by Walter de Gruyter Berlin Boston
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Articles in the same Issue
- Genes and Nucleic Acids
- The effect of cancer procoagulant on expression of metastatic and angiogenic markers in breast cancer and embryonic stem cell lines
- Characterization of RNA damage under oxidative stress in Escherichia coli
- Membranes, Lipids, Glycobiology
- Uncommon membrane distribution of Shiga toxin glycosphingolipid receptors in toxin-sensitive human glomerular microvascular endothelial cells
- Cell Biology and Signaling
- Nucleocytoplasmic shuttling of human inositol phosphate multikinase is influenced by CK2 phosphorylation
- Apolipoprotein A5 internalized by human adipocytes modulates cellular triglyceride content
- Mammalian carboxylesterase (CES) releases GPI-anchored proteins from the cell surface upon lipid raft fluidization
- Proteolysis
- Biochemical characterization and structural modeling of human cathepsin E variant 2 in comparison to the wild-type protein
- Novel Techniques
- A fluorescence correlation spectroscopy-based enzyme assay for human Dicer
- Development of a host blood meal database: de novo sequencing of hemoglobin from nine small mammals using mass spectrometry
- Prelims
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