Facing glycosphingolipid-Shiga toxin interaction: dire straits for endothelial cells of the human vasculature

被引：62

作者：

Bauwens, Andreas ^{[1
]}

Betz, Josefine ^{[1
]}

Meisen, Iris ^{[1
,2
]}

Kemper, Bjoern ^{[3
]}

Karch, Helge ^{[1
]}

Muething, Johannes ^{[1
,2
]}

机构：

[1] Univ Munster, Inst Hyg, D-48149 Munster, Germany

[2] Univ Munster, Interdisciplinary Ctr Clin Res, D-48149 Munster, Germany

[3] Univ Munster, Ctr Biomed Opt & Photon, D-48149 Munster, Germany

来源：

CELLULAR AND MOLECULAR LIFE SCIENCES | 2013年 / 70卷 / 03期

关键词：

Gb3Cer; Gb4Cer; Glycolipids; HUS; Lipid rafts; Mass spectrometry; Membrane microdomains; HEMOLYTIC-UREMIC SYNDROME; ENTEROHEMORRHAGIC ESCHERICHIA-COLI; TUMOR-NECROSIS-FACTOR; CYTOLETHAL DISTENDING TOXIN; THIN-LAYER-CHROMATOGRAPHY; DETERGENT-RESISTANT MEMBRANES; DIGITAL HOLOGRAPHIC MICROSCOPY; LIPID RAFTS; GLOBOTRIAOSYL CERAMIDE; RETROGRADE TRANSPORT;

D O I：

10.1007/s00018-012-1060-z

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：425 / 457

页数：33

共 360 条

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