I. Shiga toxin B-subunit system: retrograde transport, intracellular vectorization, and more

Johannes, Ludger

doi:10.1152/ajpgi.00088.2002

Cited by 27 publications

(16 citation statements)

References 26 publications

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“…32,[34][35][36] In our study, the quantitative determination of CD77 revealed notable concentration differences among the individual Fabry patients (2-21%), which may be caused by different a-Gal A levels, due to the great variety of a-Gal A gene mutations. In contrast to the assumption 37 that the plasma Gb3 levels reflect the Gb3 tissue load, Young 38 recently showed that Gb3 in plasma and urine cannot be used as a reliable biomarker for AFD especially in patients with the N215S mutation and many heterozygotes.…”

Section: Cd77 Expression On Cells With A-gal a Deficiencymentioning

confidence: 98%

Downregulation of α-galactosidase A upregulates CD77: functional impact for Fabry nephropathy

Thomaidis

Relle

Golbas

et al. 2009

Kidney International

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Anderson-Fabry disease, an inherited deficiency in the lysosomal enzyme alpha-galactosidase A, is characterized by the progressive accumulation of globotriaosylceramide (Gb3), also known as CD77. We sought to clarify the pathogenesis of Fabry disease by establishing a cell model of this disorder. The expression of alpha-galactosidase A was transiently silenced by RNA interference in HK2 and primary human renal epithelial cells and stably silenced in HK2 cells by retroviral transfection with small hairpin RNA. All of the silenced cells had histological similarities to cells of patients with Fabry disease. The cells had reduced viability, significant accumulation of intracellular Gb3, and a modest but significant increase in membranous Gb3 expression compared to nonsilenced cells. When silenced HK2 cells were reconstituted with agalsidase-alpha, a protein used for enzyme replacement therapy, they decreased their membranous CD77 expression to levels indistinguishable from those of nonsilenced cells. Because plasma and urinary Gb3 levels are not reliable biomarkers for Fabry disease, our study suggests that membranous CD77 levels mirror Gb3 tissue load and that CD77 expression levels may be used to monitor the efficacy of enzyme replacement therapy.

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Section: Cd77 Expression On Cells With A-gal a Deficiencymentioning

confidence: 98%

Downregulation of α-galactosidase A upregulates CD77: functional impact for Fabry nephropathy

Thomaidis

Relle

Golbas

et al. 2009

Kidney International

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“…However, a clathrin-independent mechanism mediated by lipid rafts has also been described (Johannes, 2002). The carbohydrate part, and also the fatty acid part, of Gb3 are important for toxin binding (Binnington et al, 2002).…”

Section: Intracellular Trafficking Of St and Related Toxinsmentioning

confidence: 99%

Bacterial protein toxins and lipids: role in toxin targeting and activity

Geny

Popoff

2006

Biology of the Cell

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All bacterial toxins, which globally are hydrophilic proteins, interact first with their target cells by recognizing a surface receptor, which is either a lipid or a lipid derivative, or another compound but in a lipid environment. Intracellular active toxins follow various trafficking pathways, the sorting of which is greatly dependent on the nature of the receptor, notably lipidic receptor or receptor embedded into a distinct environment such as lipid microdomains. Numerous other toxins act locally on cell membrane. Indeed, phospholipase activity is a common mechanism shared by several membrane‐damaging toxins. In addition, many toxins active intracellularly or on cell membrane modulate host cell phospholipid pathways. Unusually, a few bacterial toxins require a lipid post‐translational modification to be active. Thereby, lipids are obligate partners of bacterial toxins.

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“…To substantiate the specificity and topology of this block, we analyzed the retrograde transport routes as well. Transport kinetics of STB, known to employ a Rab6‐dependent but COPI‐independent pathway (62, 63), remained unaltered by EBAG9 expression (Fig. 11).…”

Section: Resultsmentioning

confidence: 99%

Role of EBAG9 protein in coat protein complex I‐dependent glycoprotein maturation and secretion processes in tumor cells

et al. 2010

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Many proteins mature within the secretory pathway by the acquisition of glycans. Failure to maintain the proper distribution of the glycosylation machinery might lead to disease. High expression levels of the ubiquitous Golgi protein estrogen receptor-binding fragment-associated gene 9 (EBAG9) in human tumors correlate with poor clinical prognosis, and EBAG9 overexpression in epithelial cell lines induces truncated glycans, typical of many carcinomas. Here, we addressed the pathogenetic link between EBAG9 expression and the alteration of the cellular glycome. We applied confocal microscopy, live imaging, pulse-chase labeling in conjunction with immunoprecipitation, and enzymatic activity assays in a variety of EBAG9-overexpressing or depleted epithelial tumor cell lines. EBAG9 shuttles between the ER-Golgi intermediate compartment and the cis-Golgi, and we demonstrate association of EBAG9 with coat protein complex I (COPI)-coated transport vesicles. EBAG9 overexpression imposes delay of endoplasmic reticulum-to-Golgi transport and mislocalizes components of the ER quality control and glycosylation machinery. Conversely, EBAG9 down-regulation accelerates glycoprotein transport through the Golgi and enhances mannosidase activity. Thus, EBAG9 acts as a negative regulator of a COPI-dependent ER-to-Golgi transport pathway in epithelial cells and represents a novel pathogenetic principle in which interference with intracellular membrane trafficking results in the emergence of a tumor-associated glycome.

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I. Shiga toxin B-subunit system: retrograde transport, intracellular vectorization, and more

Cited by 27 publications

References 26 publications

Downregulation of α-galactosidase A upregulates CD77: functional impact for Fabry nephropathy

Downregulation of α-galactosidase A upregulates CD77: functional impact for Fabry nephropathy

Bacterial protein toxins and lipids: role in toxin targeting and activity

Role of EBAG9 protein in coat protein complex I‐dependent glycoprotein maturation and secretion processes in tumor cells

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