title: Presenilin I expression in yeast lowers secretion of the amyloid precursor protein.
abstract: Presenilin (PS) mutations are associated with early-onset Alzheimer's disease and PS proteins are involved with gamma-secretase cleavage of the amyloid precursor protein, APP. We have shown previously that alpha-, beta- and gamma-secretase cleavages of APP are conserved in Pichia pastoris. Here, we report co-expression of APP and PSI in P. pastoris and show by immunoelectron microscopy colocalization of these two proteins in expanded endoplasmic reticulum. Western blot analysis indicates a drastic reduction of both alpha- and beta-secretase products. A relative increase in beta-secretase product derived from immature APP is also observed, pointing to a beta-secretase activity of P. pastoris associated with the early secretory pathway.
authors.affiliation: Department of Pathology, The University of Melbourne, Parkville, Victoria, Australia.
authors.forename: G
authors.initials: G
authors.lastname: Evin
authors.forename: D
authors.initials: D
authors.lastname: Le Brocque
authors.forename: J G
authors.initials: JG
authors.lastname: Culvenor
authors.forename: D
authors.initials: D
authors.lastname: Galatis
authors.forename: A
authors.initials: A
authors.lastname: Weidemann
authors.forename: K
authors.initials: K
authors.lastname: Beyreuther
authors.forename: C L
authors.initials: CL
authors.lastname: Masters
authors.forename: R
authors.initials: R
authors.lastname: Cappai
mesh_terms: D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D015153:Blotting, Western; D002999:Clone Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D010450:Endopeptidases; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006031:Glycosylation; D007150:Immunohistochemistry; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics*; D008854:Microscopy, Electron; D008954:Models, Biological; D010843:Pichia / Q000166:cytology / Q000201:enzymology* / Q000235:genetics* / Q000648:ultrastructure; D053764:Presenilin-1; D011499:Protein Processing, Post-Translational; D014162:Transfection
chemical_list: D016564:Amyloid beta-Protein Precursor; D008565:Membrane Proteins; D053764:Presenilin-1; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases