title: Generation of Alzheimer beta-amyloid protein in the trans-Golgi network in the apparent absence of vesicle formation.
abstract: 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.
authors.affiliation: Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021, USA.
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.forename: D
authors.initials: D
authors.lastname: Sweeney
authors.forename: R
authors.initials: R
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Thinakaran
authors.forename: A C
authors.initials: AC
authors.lastname: Lo
authors.forename: S S
authors.initials: SS
authors.lastname: Sisodia
authors.forename: P
authors.initials: P
authors.lastname: Greengard
authors.forename: S
authors.initials: S
authors.lastname: Gandy
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001692:Biological Transport; D002460:Cell Line; D003594:Cytoplasmic Granules / Q000378:metabolism* / Q000648:ultrastructure; D006056:Golgi Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans
chemical_list: D016229:Amyloid beta-Peptides