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Golgi function and dysfunction in the first COG4-deficient CDG type II patient
The conserved oligomeric Golgi (COG) complex is a hetero-octameric complex essential for normal glycosylation and intra-Golgi transport. An increasing number of congenital disorder of glycosylation type II (CDG-II) mutations are found in COG subunits indicating its importance in glycosylation. We re...
Autores principales: | , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722986/ https://www.ncbi.nlm.nih.gov/pubmed/19494034 http://dx.doi.org/10.1093/hmg/ddp262 |
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author | Reynders, Ellen Foulquier, François Leão Teles, Elisa Quelhas, Dulce Morelle, Willy Rabouille, Cathérine Annaert, Wim Matthijs, Gert |
author_facet | Reynders, Ellen Foulquier, François Leão Teles, Elisa Quelhas, Dulce Morelle, Willy Rabouille, Cathérine Annaert, Wim Matthijs, Gert |
author_sort | Reynders, Ellen |
collection | PubMed |
description | The conserved oligomeric Golgi (COG) complex is a hetero-octameric complex essential for normal glycosylation and intra-Golgi transport. An increasing number of congenital disorder of glycosylation type II (CDG-II) mutations are found in COG subunits indicating its importance in glycosylation. We report a new CDG-II patient harbouring a p.R729W missense mutation in COG4 combined with a submicroscopical deletion. The resulting downregulation of COG4 expression additionally affects expression or stability of other lobe A subunits. Despite this, full complex formation was maintained albeit to a lower extent as shown by glycerol gradient centrifugation. Moreover, our data indicate that subunits are present in a cytosolic pool and full complex formation assists tethering preceding membrane fusion. By extending this study to four other known COG-deficient patients, we now present the first comparative analysis on defects in transport, glycosylation and Golgi ultrastructure in these patients. The observed structural and biochemical abnormalities correlate with the severity of the mutation, with the COG4 mutant being the mildest. All together our results indicate that intact COG complexes are required to maintain Golgi dynamics and its associated functions. According to the current CDG nomenclature, this newly identified deficiency is designated CDG-IIj. |
format | Text |
id | pubmed-2722986 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-27229862009-08-07 Golgi function and dysfunction in the first COG4-deficient CDG type II patient Reynders, Ellen Foulquier, François Leão Teles, Elisa Quelhas, Dulce Morelle, Willy Rabouille, Cathérine Annaert, Wim Matthijs, Gert Hum Mol Genet Articles The conserved oligomeric Golgi (COG) complex is a hetero-octameric complex essential for normal glycosylation and intra-Golgi transport. An increasing number of congenital disorder of glycosylation type II (CDG-II) mutations are found in COG subunits indicating its importance in glycosylation. We report a new CDG-II patient harbouring a p.R729W missense mutation in COG4 combined with a submicroscopical deletion. The resulting downregulation of COG4 expression additionally affects expression or stability of other lobe A subunits. Despite this, full complex formation was maintained albeit to a lower extent as shown by glycerol gradient centrifugation. Moreover, our data indicate that subunits are present in a cytosolic pool and full complex formation assists tethering preceding membrane fusion. By extending this study to four other known COG-deficient patients, we now present the first comparative analysis on defects in transport, glycosylation and Golgi ultrastructure in these patients. The observed structural and biochemical abnormalities correlate with the severity of the mutation, with the COG4 mutant being the mildest. All together our results indicate that intact COG complexes are required to maintain Golgi dynamics and its associated functions. According to the current CDG nomenclature, this newly identified deficiency is designated CDG-IIj. Oxford University Press 2009-09-01 2009-06-03 /pmc/articles/PMC2722986/ /pubmed/19494034 http://dx.doi.org/10.1093/hmg/ddp262 Text en © 2009 The Author(s) http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Articles Reynders, Ellen Foulquier, François Leão Teles, Elisa Quelhas, Dulce Morelle, Willy Rabouille, Cathérine Annaert, Wim Matthijs, Gert Golgi function and dysfunction in the first COG4-deficient CDG type II patient |
title | Golgi function and dysfunction in the first COG4-deficient CDG type II patient |
title_full | Golgi function and dysfunction in the first COG4-deficient CDG type II patient |
title_fullStr | Golgi function and dysfunction in the first COG4-deficient CDG type II patient |
title_full_unstemmed | Golgi function and dysfunction in the first COG4-deficient CDG type II patient |
title_short | Golgi function and dysfunction in the first COG4-deficient CDG type II patient |
title_sort | golgi function and dysfunction in the first cog4-deficient cdg type ii patient |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722986/ https://www.ncbi.nlm.nih.gov/pubmed/19494034 http://dx.doi.org/10.1093/hmg/ddp262 |
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