title: The over-expression of the wild type or mutant forms of the presenilin-1 protein alters glycoprotein processing in a human neuroblastoma cell line.
abstract: Mutations in the presenilin proteins (PS1 and PS2) are responsible for more than 70% of the cases of the familial form of Alzheimer's disease (FAD). The proteins are expressed in the cell at a low level, primarily in the endoplasmic reticulum and cis Golgi, where they have been proposed to play a role in protein processing. As protein glycosylation is a key post-translational event that occurs within the Golgi, we have investigated the effect of altered PS1 expression levels on the protein glycosylation pattern using the SH-SY5Y human neuroblastoma cell line. In cells over-expressing either the wild type or mutant (M146L) PS1-FAD proteins, there was a decrease in the expression levels of protein-bound alpha2,3-linked sialic acid residues at the level of the cell membrane. This was particularly manifest as a significant decrease in the expression of the polysialic acid chain that is linked to the core oligosaccharide of the neural cell adhesion molecule in an alpha2,3 bond. These results suggest that the over-expression of either the wild type or mutant PS1 disturbs glycoprotein processing within the Golgi.
authors.affiliation: Department of Psychiatry, University of Dundee, Ninewells Hospital Medical School, Dundee DD1 9SY, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Farquhar
authors.forename: C W
authors.initials: CW
authors.lastname: Gray
authors.forename: K C
authors.initials: KC
authors.lastname: Breen
mesh_terms: D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D009154:Mutation / Q000502:physiology*; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism*; D053764:Presenilin-1; D014407:Tumor Cells, Cultured
chemical_list: D006023:Glycoproteins; D008565:Membrane Proteins; D019006:Neural Cell Adhesion Molecules; C508853:PSEN1 protein, human; D053764:Presenilin-1