Golgi function and dysfunction in the first COG4-deficient CDG type II patient
Identifieur interne : 000119 ( France/Analysis ); précédent : 000118; suivant : 000120Golgi function and dysfunction in the first COG4-deficient CDG type II patient
Auteurs : Ellen Reynders [Belgique] ; Franois Foulquier [France] ; Elisa Leo Teles [Portugal] ; Dulce Quelhas [Portugal] ; Willy Morelle [France] ; Cathrine Rabouille [Pays-Bas] ; Wim Annaert [Belgique] ; Gert Matthijs [Belgique]Source :
- Human Molecular Genetics [ 0964-6906 ] ; 2009-09-01.
Abstract
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.
Url:
DOI: 10.1093/hmg/ddp262
Affiliations:
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ISTEX:831D37947AD7F17B4C21665F43821EEFDD165D9ALe document en format XML
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Genetics</title><idno type="ISSN">0964-6906</idno><idno type="eISSN">1460-2083</idno><imprint><publisher>Oxford University Press</publisher><date type="published" when="2009-09-01">2009-09-01</date><biblScope unit="volume">18</biblScope><biblScope unit="issue">17</biblScope><biblScope unit="page" from="3244">3244</biblScope><biblScope unit="page" to="3256">3256</biblScope></imprint><idno type="ISSN">0964-6906</idno></series><idno type="istex">831D37947AD7F17B4C21665F43821EEFDD165D9A</idno><idno type="DOI">10.1093/hmg/ddp262</idno><idno type="ArticleID">ddp262</idno></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0964-6906</idno></seriesStmt></fileDesc><profileDesc><textClass></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract">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.</div></front></TEI><affiliations><list><country><li>Belgique</li><li>France</li><li>Pays-Bas</li><li>Portugal</li></country><region><li>Utrecht (province)</li></region><settlement><li>Lille</li><li>Utrecht</li></settlement></list><tree><country name="Belgique"><noRegion><name sortKey="Reynders, Ellen" sort="Reynders, Ellen" uniqKey="Reynders E" first="Ellen" last="Reynders">Ellen Reynders</name></noRegion><name sortKey="Annaert, Wim" sort="Annaert, Wim" uniqKey="Annaert W" first="Wim" last="Annaert">Wim Annaert</name><name sortKey="Annaert, Wim" sort="Annaert, Wim" uniqKey="Annaert W" first="Wim" last="Annaert">Wim Annaert</name><name sortKey="Matthijs, Gert" sort="Matthijs, Gert" uniqKey="Matthijs G" first="Gert" last="Matthijs">Gert Matthijs</name><name sortKey="Matthijs, Gert" sort="Matthijs, Gert" uniqKey="Matthijs G" first="Gert" last="Matthijs">Gert Matthijs</name></country><country name="France"><noRegion><name sortKey="Foulquier, Franois" sort="Foulquier, Franois" uniqKey="Foulquier F" first="Franois" last="Foulquier">Franois Foulquier</name></noRegion><name sortKey="Morelle, Willy" sort="Morelle, Willy" uniqKey="Morelle W" first="Willy" last="Morelle">Willy Morelle</name></country><country name="Portugal"><noRegion><name sortKey="Leo Teles, Elisa" sort="Leo Teles, Elisa" uniqKey="Leo Teles E" first="Elisa" last="Leo Teles">Elisa Leo Teles</name></noRegion><name sortKey="Quelhas, Dulce" sort="Quelhas, Dulce" uniqKey="Quelhas D" first="Dulce" last="Quelhas">Dulce Quelhas</name></country><country name="Pays-Bas"><region name="Utrecht (province)"><name sortKey="Rabouille, Cathrine" sort="Rabouille, Cathrine" uniqKey="Rabouille C" first="Cathrine" last="Rabouille">Cathrine Rabouille</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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