Send to

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3748-52.

Generation of Alzheimer beta-amyloid protein in the trans-Golgi network in the apparent absence of vesicle formation.

Author information

  • 1Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021, USA.


beta-amyloid protein (A beta) formation was reconstituted in permeabilized neuroblastoma cells expressing human Alzheimer beta-amyloid precursor protein (beta APP) harboring the Swedish double mutation associated with familial early-onset Alzheimer disease. Permeabilized cells were prepared following metabolic labeling and incubation at 20 degrees C, a temperature that allows beta APP to accumulate in the trans-Golgi network (TGN) without concomitant A beta formation. Subsequent incubation at 37 degrees C led to the generation of A beta. A beta production in the TGN persisted even under conditions in which formation of nascent post-TGN vesicles was inhibited by addition of guanosine 5'-O-(3-thiotriphosphate), a nonhydrolyzable GTP analogue, or by omission of cytosol. These and other results indicate that vesicle budding and trafficking may not be required for proteolytic metabolism of beta APP to A beta, a process that includes "gamma-secretase" cleavage within the beta APP transmembrane domain.

[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center