Document Detail

Shiga toxins, glycosphingolipid diversity, and endothelial cell injury.
MedLine Citation:
PMID:  19190807     Owner:  NLM     Status:  MEDLINE    
Shiga toxin (Stx)-producing Escherichia coli (STEC) cause an enteric illness that results in a spectrum of outcomes ranging from asymptomatic carriage to uncomplicated diarrhea, bloody diarrhea, and the postdiarrheal haemolytic uremic syndrome (HUS), which leads to renal and other organ microvascular thrombosis. Binding of Stx to the glycosphingolipid (GSL) globotriaosylceramide (Gb3Cer/CD77) on endothelial cells followed by receptor-mediated endocytosis is the linchpin in STEC-mediated disease. Only GSLs that associate strongly with lipid rafts appear to carry Stxs retrogradely from the plasma membrane through the Golgi apparatus to the endoplasmic reticulum where they are translocated to the cytosol and exert their toxic function. Thus, the biophysical features of the lipid moiety of GSL receptors may influence its incorporation into certain membrane domains and thereby affect toxin destination. Consequently, a detailed structural analysis of Stx-binding GSLs is required to illuminate the molecular causes that may underlie the different Stx susceptibilities of endothelial cells derived from various vascular beds. Solid phase overlay binding assays of thin-layer chromatography (TLC)-separated GSL preparations employing specific antibodies and/or Stxs in conjunction with anti-Stx-antibodies are commonly used for the identification of Stx-binding GSLs. Such GSL-profiling combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) represents a convenient strategy to structurally characterize Stx-receptors from any biological sources such as primary cells, cell lines, or organs. This approach may be helpful to gain insights into Stx-induced impairment of target cells that is suggested to originate at least partly from the structural heterogeneity of the cellular ligands of Stxs.
Johannes Müthing; Christian H Schweppe; Helge Karch; Alexander W Friedrich
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Thrombosis and haemostasis     Volume:  101     ISSN:  0340-6245     ISO Abbreviation:  Thromb. Haemost.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-02-04     Completed Date:  2009-03-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7608063     Medline TA:  Thromb Haemost     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  252-64     Citation Subset:  IM    
Institut für Hygiene, Universitätsklinikum Münster, Robert-Koch-Str. 41, 48149 Münster, Germany.
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MeSH Terms
Amino Acid Sequence
Chromatography, Thin Layer
Endothelium, Vascular / metabolism*,  microbiology,  pathology
Escherichia coli Infections / metabolism,  microbiology*,  pathology
Hemolytic-Uremic Syndrome / metabolism,  microbiology*,  pathology
Membrane Microdomains / metabolism,  microbiology
Molecular Sequence Data
Peptide Mapping
Protein Conformation
Protein Subunits
Protein Transport
Proteomics / methods
Shiga Toxins / chemistry,  metabolism*
Shiga-Toxigenic Escherichia coli / metabolism,  pathogenicity*
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Structure-Activity Relationship
Trihexosylceramides / metabolism*
Reg. No./Substance:
0/Ligands; 0/Protein Subunits; 0/Shiga Toxins; 0/Trihexosylceramides; 71965-57-6/globotriaosylceramide

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