IMR Press / FBL / Volume 6 / Issue 3 / DOI: 10.2741/gouyer

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.


Inhibition of the glycosylation and alteration in the intracellular trafficking of mucins and other glycoproteins by GalNAcα-O-bn in mucosal cell lines: an effect mediated through the intracellular synthesis of complex GalNAcα-O-bn oligosaccharides

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1 Unite INSERM 377, Place de Verdun, 59045 Lille cedex, France
2 Unité de Glycobiologie structurale et fonctionnelle, UMR CNRS n°8576, Laboratoire de chimie biologique, Université des sciences et technologies de Lille, F-59655 Villeneuve d’Ascq
3 Unité INSERM 505, 15 rue de l’école de Médecine, 75006 Paris, France
Front. Biosci. (Landmark Ed) 2001, 6(3), 1235–1244;
Published: 1 October 2001

To address the function of carbohydrates in mucins, GalNAcα-O-bn has been used in in vivo experiments on several human mucosal cultured cells as a potential competitor of the glycosylation of N-acetylgalactosamine residues. GalNAcα-O-bn is metabolized by glycosyltransferases expressed in the cell, and give rise to different internal derivatives starting in particular from the formation of the disaccharide Galβ1-3GalNAcα-O-bn. In this line, GalNAcα-O-bn exposure inhibits peripheral glycosylation according a cell-type specific manner. The metabolic alterations are very important in HT-29 cell line, leading to a massive accumulation of GalNAcα-O-bn oligosaccharide derivatives and to a strong inhibition of the terminal elongation of O-glycans by α2,3 sialyltransferase ST3Gal I. GalNAcα-O-bn treatment also induced alterations at the cellular level, exhibiting a large scale in HT-29 cells, i.e. 1) an inhibition of mucin secretion, 2) a blockade in the targeting of some membrane glycoproteins (brush border glycoproteins such as dipeptidylpeptidase IV, carcinoembryonic antigen and the mucin-like glycoprotein MUC1, and the basolateral cell adhesion molecule CD44), 3) an inhibition in the processing of lysosomal enzymes. Morphological abnormalities have been evidenced in GalNAcα-O-bn treated cells, in particular the accumulation of numerous intracellular vesicles in HT-29 cells. Taken together, these data suggest that O-glycosylation might be involved in the regulation of the targeting of O-glycosylproteins through carrier vesicles.

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