|
||
J. Cell Biol.,
Volume 141, Number 6, June 15, 1998 1311-1322
-O-benzyl Inhibits NeuAc
2-3 Glycosylation and
Blocks the Intracellular Transport of Apical Glycoproteins
and Mucus in Differentiated HT-29 Cells





* Unité de Recherches sur la Biologie et la Physiopathologie des Cellules Mucipares, Institut National de la Sante et de la
Recherche Medicale (INSERM) U377, 59045 Lille Cedex, France; Exposure for 24 h of mucus-secreting HT-29
cells to the sugar analogue GalNAc-
Unitat de Biologia Cellular i Molecular, Institut Municipal
d'Investigació Mèdica, Universitat Autónoma de Barcelona, E-08003, Barcelona, Spain; § Unité de Recherches sur la
Différenciation Cellulaire Intestinale, INSERM U178, 94807 Villejuif Cedex, France; and
Laboratoire de Chimie Biologique,
Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR)-111, Université des Sciences et
Technologies de Lille, 59655 Villeneuve d'Ascq Cedex, France
-O-benzyl results
in inhibition of Gal
1-3GalNAc:
2,3-sialyltransferase, reduced mucin sialylation, and inhibition of their secretion (Huet, G., I. Kim, C. de Bolos, J.M. Loguidice, O. Moreau, B. Hémon, C. Richet, P. Delannoy, F.X. Real.,
and P. Degand. 1995. J. Cell Sci. 108:1275-1285). To determine the effects of prolonged inhibition of sialylation, differentiated HT-29 populations were grown under permanent exposure to GalNAc-
-O-benzyl. This
results in not only inhibition of mucus secretion, but
also in a dramatic swelling of the cells and the accumulation in intracytoplasmic vesicles of brush border-associated glycoproteins like dipeptidylpeptidase-IV, the
mucin-like glycoprotein MUC1, and carcinoembryonic
antigen which are no longer expressed at the apical
membrane. The block occurs beyond the cis-Golgi as
substantiated by endoglycosidase treatment and biosynthesis analysis. In contrast, the polarized expression
of the basolateral glycoprotein GP 120 is not modified. Underlying these effects we found that (a) like in mucins, NeuAc
2-3Gal-R is expressed in the terminal position of the oligosaccharide species associated with the
apical, but not the basolateral glycoproteins of the cells,
and (b) treatment with GalNAc-
-O-benzyl results in
an impairment of their sialylation. These effects are reversible upon removal of the drug. It is suggested that
2-3 sialylation is involved in apical targeting of brush
border membrane glycoproteins and mucus secretion in
HT-29 cells.
This article has been cited by other articles:
|
|