This item still needs to be validated !
Title: Study of the synthesis and secretion of normal and artificial mutants of murine amyloid precursor protein (APP): cleavage of APP occurs in a late compartment of the default secretion pathway
Authors: De Strooper, Bart ×
Umans, L
Van Leuven, Freddy
Van den Berghe, Herman #
Issue Date: May-1993
Series Title: Journal of Cell Biology vol:121 issue:2 pages:295-304
Abstract: Amyloid precursor protein (APP) secretase plays a pivotal role in the processing of APP since its activity precludes the formation of amyloid peptide in Alzheimer's Disease. The identity and the subcellular localization of this enzyme are at this moment unknown. It is also unclear how APP escapes the activity of this enzyme when amyloid is formed. We have previously shown that APP-secretase activity is not inhibited by exogenously added proteinase inhibitors of different specificity (De Strooper, B., F. Van Leuven, and H. Van Den Berghe. 1992. FEBS (Fed. Eur. Biochem. Soc.) Lett. 308:50-53). We show here that the primary amine methylamine inhibits the secretion of APP into the medium. Furthermore, we show that a truncated form of APP, devoid of the cytoplasmic domain, is more efficiently cleaved and secreted than wild-type APP, which together with the methylamine block, shows that APP-secretase is located in a late compartment of the default constitutional secretion pathway. The sorting signals in the cytoplasmic domain of APP are therefore important in the deviation of APP from the secretase pathway. Finally we show that mutation of Arg609 to Asp in combination with Lys612 to Glu makes APP a less efficiently cleaved substrate for APP-secretase. The results are discussed in the context of recent findings on the targeting of APP and a parallel is drawn with some lysosomal glycoproteins that follow similar pathways.
ISSN: 0021-9525
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Genetics Section (-)
Associated Laboratories - miscellaneous (-)
Clinical Genetics Section (-)
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