title: Golgi function and dysfunction in the first COG4-deficient CDG type II patient.
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.
authors.affiliation: and Department for Molecular and Developmental Genetics, Laboratory for Membrane Trafficking, Center for Human Genetics, University of Leuven VIB, B-3000 Leuven, Belgium.
authors.forename: Ellen
authors.initials: E
authors.lastname: Reynders
authors.forename: François
authors.initials: F
authors.lastname: Foulquier
authors.forename: Elisa
authors.initials: E
authors.lastname: Leão Teles
authors.forename: Dulce
authors.initials: D
authors.lastname: Quelhas
authors.forename: Willy
authors.initials: W
authors.lastname: Morelle
authors.forename: Cathérine
authors.initials: C
authors.lastname: Rabouille
authors.forename: Wim
authors.initials: W
authors.lastname: Annaert
authors.forename: Gert
authors.initials: G
authors.lastname: Matthijs
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D002239:Carbohydrate Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002675:Child, Preschool; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006031:Glycosylation; D006056:Golgi Apparatus / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D021381:Protein Transport; D017386:Sequence Homology, Amino Acid; D033921:Vesicular Transport Proteins
chemical_list: C542474:COG4 protein, human; D002352:Carrier Proteins; D033921:Vesicular Transport Proteins