Journal
JOURNAL OF MOLECULAR NEUROSCIENCE
Volume 19, Issue 1-2, Pages 31-35Publisher
HUMANA PRESS INC
DOI: 10.1007/s12031-002-0007-5
Keywords
Alzheimer's disease; amyloid; secretase; lipid rafts; DIGs; TIMs; glycosylphosphatidylinositol; GPI-anchored protein
Categories
Ask authors/readers for more resources
The Alzheimer's amyloid beta protein (Abeta) precursor (APP) is proteolytically cleaved by beta-secretase to N- and C-terminal fragments sAPPbeta and CTFbeta, respectively. Subsequently, CTFbeta is cleaved by gamma-secretase to generate Abeta. We previously showed that the levels of secreted Abeta and sAPPbeta were significantly reduced upon removal of glycosylphosphatidylinositol (GPI)-anchored proteins from either primary brain cells or Chinese hamster ovary cultures. The results indicated that GPI-anchored proteins facilitated beta-secretase activity. In this report, we strengthen the previous findings by demonstrating that CTFbeta, like sAPPbeta, is also reduced upon removal of GPI-anchored proteins and that sAPPbeta does not accumulate in an intracellular compartment. This facilitation pathway does not appear to be important for the processing of a disease-linked mutant form of APP (670NL), known to be a superior beta-secretase substrate. A novel aspartyl protease, BACE, responsible for beta-secretase activity in the brain is not GPI-anchored. However, BACE in brain membranes accumulate in lipid rafts, a compartment marked by the accumulation of GPI-anchored proteins. This finding is consistent with the hypothesis that BACE interacts with GPI-anchored proteins that facilitate its activity possibly by chaperoning it into lipid rafts.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available