This item still needs to be validated !
Title: Phosphorylation, subcellular localization, and membrane orientation of the Alzheimer's disease-associated presenilins
Authors: De Strooper, Bart ×
Beullens, Monique
Contreras, Bart
Levesque, L
Craessaerts, Kathleen
Cordell, B
Moechars, Diederik
Bollen, Mathieu
George-Hyslop, P S
Van Leuven, Freddy #
Issue Date: Feb-1997
Series Title: Journal of Biological Chemistry vol:272 issue:6 pages:3590-8
Abstract: Presenilins 1 and 2 are unglycosylated proteins with apparent molecular mass of 45 and 50 kDa, respectively, in transfected COS-1 and Chinese hamster ovary cells. They colocalize with proteins from the endoplasmic reticulum and the Golgi apparatus in transfected and untransfected cells. In COS-1 cells low amounts of intact endogeneous presenilin 1 migrating at 45 kDa are detected together with relative larger amounts of presenilin 1 fragments migrating between 18 and 30 kDa. The presenilins have a strong tendency to form aggregates (mass of 100-250 kDa) in SDS-polyacrylamide gel electrophoresis, which can be partially resolved when denatured by SDS at 37 degrees C instead of 95 degrees C. Sulfation, glycosaminoglycan modification, or acylation of the presenilins was not observed, but both proteins are posttranslationally phosphorylated on serine residues. The mutations Ala-246 --> Glu or Cys-410 --> Tyr that cause Alzheimer's disease do not interfere with the biosynthesis or phosphorylation of presenilin 1. Finally, using low concentrations of digitonin to selectively permeabilize the cell membrane but not the endoplasmic reticulum membrane, it is demonstrated that the two major hydrophilic domains of presenilin 1 are oriented to the cytoplasm. The current investigation documents the posttranslational modifications and subcellular localization of the presenilins and indicates that postulated interactions with amyloid precursor protein metabolism should occur in the early compartments of the biosynthetic pathway.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Genetics Section (-)
Biochemistry Section (Medicine) (-)
Associated Laboratories - miscellaneous (-)
Laboratory of Biosignaling & Therapeutics
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science