Please use this identifier to cite or link to this item: https://doi.org/10.21256/zhaw-3989
Title: Differential effects of lobe A and lobe B of the conserved oligomeric golgi complex on the stability of β1,4-galactosyltransferase 1 and α2,6-sialyltransferase 1
Authors : Peanne, Romain
Legrand, Dominique
Duvet, Sandrine
Mir, Anne-Marie
Matthijs, Gert
Rohrer, Jack
Foulquier, Francois
Published in : Glycobiology
Volume(Issue) : 21
Issue : 7
Pages : 864
Pages to: 876
Publisher / Ed. Institution : Oxford University Press
Issue Date: 8-Nov-2011
License (according to publishing contract) : Licence according to publishing contract
Type of review: Peer review (Publication)
Language : English
Subject (DDC) : 572: Biochemistry
Abstract: Initially described by Jaeken et al. in 1980, congenital disorders of glycosylation (CDG) is a rapidly expanding group of human multisystemic disorders. To date, many CDG patients have been identified with deficiencies in the conserved oligomeric Golgi (COG) complex which is a complex involved in the vesicular intra-Golgi retrograde trafficking. Composed of eight subunits that are organized in two lobes, COG subunit deficiencies have been associated with Golgi glycosylation abnormalities. Analysis of the total serum N-glycans of COG-deficient CDG patients demonstrated an overall decrease in terminal sialylation and galactosylation. According to the mutated COG subunits, differences in late Golgi glycosylation were observed and led us to address the question of an independent role and requirement for each of the two lobes of the COG complex in the stability and localization of late terminal Golgi glycosylation enzymes. For this, we used a small-interfering RNAs strategy in HeLa cells stably expressing green fluorescent protein (GFP)-tagged β1,4-galactosyltransferase 1 (B4GALT1) and α2,6-sialyltransferase 1 (ST6GAL1), two major Golgi glycosyltransferases involved in late Golgi N-glycosylation. Using fluorescent lectins and flow cytometry analysis, we clearly demonstrated that depletion of both lobes was associated with deficiencies in terminal Golgi N-glycosylation. Lobe A depletion resulted in dramatic changes in the Golgi structure, whereas lobe B depletion severely altered the stability of B4GALT1 and ST6GAL1. Only MG132 was able to rescue their steady-state levels, suggesting that B4GALT1- and ST6GAL1-induced degradation are likely the consequence of an accumulation in the endoplasmic reticulum (ER), followed by a retrotranslocation into the cytosol and proteasomal degradation. All together, our results suggest differential effects of lobe A and lobe B for the localization/stability of B4GALT1 and ST6GAL1. Lobe B would be crucial in preventing these two Golgi glycosyltransferases from inappropriate retrograde trafficking to the ER, whereas lobe A appears to be essential for maintaining the overall Golgi structure.
Further description : Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch)
Departement: Life Sciences und Facility Management
Organisational Unit: Institute of Chemistry and Biotechnology (ICBT)
Publication type: Article in scientific Journal
DOI : 10.1093/glycob/cwq176
10.21256/zhaw-3989
ISSN: 0959-6658
URI: https://digitalcollection.zhaw.ch/handle/11475/6816
Appears in Collections:Publikationen Life Sciences und Facility Management

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