Ludwig-Maximilians-Universität, Chair of Metabolic Biochemistry
print


Breadcrumb Navigation


Content

Reconstitution of gamma-secretase activity

Nat Cell Biol 5(5): 486-8

Authors/Editors: Edbauer D
Winkler E
Regula JT
Pesold B
Steiner H
Haass C
Publication Date: 2003
Type of Publication: Journal Article
gamma-Secretase is a membrane protein complex with an unusual aspartyl protease activity that catalyses the regulated intramembranous cleavage of the beta-amyloid precursor protein (APP) to release the Alzheimer's disease (AD)-associated amyloid beta-peptide (Abeta) and the APP intracellular domain (AICD). Here we show the reconstitution of gamma-secretase activity in the yeast Saccharomyces cerevisiae, which lacks endogenous gamma-secretase activity. Reconstituted gamma-secretase activity depends on the presence of four complex components including presenilin (PS), nicastrin (Nct), APH-1 (refs 3-6) and PEN-2 (refs 4, 7), is associated with endoproteolysis of PS, and produces Abeta and AICD in vitro. Thus, the biological activity of gamma-secretase is reconstituted by the co-expression of human PS, Nct, APH-1 and PEN-2 in yeast.

Related Links