GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing
| Autor: | Meihua Deng, Robert Spoelgen, Mirjam Koker, Toshifumi Matsui, Michael C. Irizarry, Stefan F. Lichtenthaler, Christine A F Von Arnim, Hisatomo Kowa, Stephanie L. Courchesne, Ithan D. Peltan, Bradley T. Hyman |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Glycosylation
Protein family Amyloid beta Recombinant Fusion Proteins Golgi Apparatus Kidney Transfection Cell Line symbols.namesake Amyloid beta-Protein Precursor Mice Neuroblastoma Structure-Activity Relationship Protein structure Cell Line Tumor mental disorders Amyloid precursor protein GGA1 Fluorescence Resonance Energy Transfer Animals Aspartic Acid Endopeptidases Humans Sequence Deletion Brain Chemistry biology ADP-Ribosylation Factors General Neuroscience P3 peptide Signal transducing adaptor protein Articles Golgi apparatus Peptide Fragments Cell biology Protein Structure Tertiary Adaptor Proteins Vesicular Transport Protein Transport Biochemistry biology.protein symbols Amyloid Precursor Protein Secretases Protein Processing Post-Translational |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 26(39) |
| ISSN: | 1529-2401 |
| Popis: | The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD. |
| Databáze: | OpenAIRE |
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