title: Mutation of potential N-linked glycosylation sites in the Alzheimer's disease amyloid precursor protein (APP).
abstract: In order to study the mechanism of intracellular sorting and processing of the Alzheimer's disease amyloid precursor protein (APP), we deleted two potential N-linked glycosylation sites of APP by site-directed mutagenesis. Substitution of alanines for the critical asparagine residues Asn467 and Asn496 was performed. Wild-type and mutant APPs were expressed in COS-1 cells by cDNA transfection and the expressed of the protein and secretion of N-terminal large fragment was observed. The initial secretion of the mutant APP appeared to be slow compared with wild-type. In addition, we found that a distinct APP fragment, the cytosolic form, is transiently increased in the cytosol fraction of COS-1 cells. These results suggest that aberrant processing occurs following the expression of a mutant APP with Ala substituted for Asn, and that glycosylation may modulate the intracellular sorting of APP.
authors.affiliation: Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yazaki
authors.forename: K
authors.initials: K
authors.lastname: Tagawa
authors.forename: K
authors.initials: K
authors.lastname: Maruyama
authors.forename: H
authors.initials: H
authors.lastname: Sorimachi
authors.forename: T
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: S
authors.initials: S
authors.lastname: Ishiura
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D019556:COS Cells / Q000502:physiology; D018076:DNA, Complementary; D004591:Electrophoresis, Polyacrylamide Gel; D015870:Gene Expression / Q000502:physiology; D006031:Glycosylation; D007700:Kinetics; D008970:Molecular Weight; D016296:Mutagenesis / Q000502:physiology; D013347:Subcellular Fractions / Q000737:chemistry
chemical_list: D016564:Amyloid beta-Protein Precursor; D018076:DNA, Complementary