Generation of Alzheimer beta-amyloid protein in the trans-Golgi network in the apparent absence of vesicle formation
| Autor: | Huaxi Xu, David Sweeney, Gopal Thinakaran, Paul Greengard, Sam Gandy, Sangram S. Sisodia, Rong Wang, Amy C. Y. Lo |
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| Rok vydání: | 1997 |
| Předmět: |
Multidisciplinary
Amyloid beta-Peptides GTP' Vesicle Guanosine Golgi Apparatus - Metabolism - Ultrastructure Golgi Apparatus Biological Transport Golgi apparatus Biology Biological Sciences Cleavage (embryo) Cytoplasmic Granules Cell biology Cell Line Cytosol symbols.namesake Transmembrane domain chemistry.chemical_compound chemistry Cell culture symbols Humans Amyloid Beta-Peptides - Metabolism Cytoplasmic Granules - Metabolism - Ultrastructure |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 94(8) |
| ISSN: | 0027-8424 |
| Popis: | β-amyloid protein (Aβ) formation was reconstituted in permeabilized neuroblastoma cells expressing human Alzheimer β-amyloid precursor protein (βAPP) harboring the Swedish double mutation associated with familial early- onset Alzheimer disease. Permeabilized cells were prepared following metabolic labeling and incubation at 20°C, a temperature that allows βAPP to accumulate in the trans-Golgi network (TGN) without concomitant Aβ formation. Subsequent incubation at 37°C led to the generation of Aβ. Aβ 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 βAPP to Aβ, a process that includes 'γ-secretase' cleavage within the βAPP transmembrane domain. link_to_OA_fulltext |
| Databáze: | OpenAIRE |
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