Document Detail


Perturbation of free oligosaccharide trafficking in endoplasmic reticulum glucosidase I-deficient and castanospermine-treated cells.
MedLine Citation:
PMID:  11942856     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Free oligosaccharides (FOS) are generated both in the endoplasmic reticulum (ER) and in the cytosol during glycoprotein biosynthesis. ER lumenal FOS possessing the di-N-acetylchitobiose moiety at their reducing termini (FOSGN2) are exported into the cytosol where they, along with their cytosolically generated counterparts possessing a single N-acetylglucosamine residue at their reducing termini (FOSGN1), are trimmed in order to be imported into lysosomes for final degradation. Both the ER and lysosomal FOS transport processes are unable to translocate triglucosylated FOS across membranes. In the present study, we have examined FOS trafficking in HepG2 cells treated with the glucosidase inhibitor castanospermine. We have shown that triglucosylated FOSGN2 generated in the ER are transported to the Golgi apparatus where they are deglucosylated by endomannosidase and acquire complex, sialic acid-containing structures before being secreted into the extracellular space by a Brefeldin A-sensitive pathway. FOSGN2 are also secreted from glucosidase I-deficient Lec23 cells and from the castanospermine-treated parental Chinese-hamster ovary cell line. Despite the secretion of FOSGN2 from Lec23 cells, we noted a transient intracellular accumulation (60 nmol/g cells) of triglucosylated FOSGN1 in these cells. Finally, in glucosidase I-compromised cells, FOS trafficking was severely perturbed leading to both the secretion of FOSGN2 into the extracellular space and a growth-dependent pile up of triglucosylated FOSGN1 in the cytosol. The possibility that these abnormalities contributed to the severe and rapidly progressive pathology in a patient with congenital disorders of glycosylation type IIb (glucosidase I deficiency) is discussed.
Authors:
Christelle Durrant; Stuart E H Moore
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  365     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-06-19     Completed Date:  2002-07-26     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  239-47     Citation Subset:  IM    
Affiliation:
Unité de Glycobiologie et Signalisation Cellulaire, U504, Bâtiment INSERM, 16 avenue Paul Vaillant-Couturier, 94807 Villejuif Cedex, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
CHO Cells
Cell Line
Cricetinae
Endoplasmic Reticulum / drug effects,  metabolism*
Enzyme Inhibitors / pharmacology
Glycogen Storage Disease Type II / metabolism
Humans
Indolizines / pharmacology
Oligosaccharides / chemistry,  isolation & purification,  metabolism*
alpha-Glucosidases / antagonists & inhibitors,  deficiency*,  metabolism
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Indolizines; 0/Oligosaccharides; 79831-76-8/castanospermine; EC 3.2.1.-/glucosidase I; EC 3.2.1.20/alpha-Glucosidases
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