Amyloid precursor protein accumulates in aggresomes in response to proteasome inhibitor
| Autor: | Annica Rönnbäck, Caroline Graff, Johanna Enö Persson, Tore Bengtsson, Homira Behbahani, Nodi Dehvari, Tapan Mahmud, Bengt Winblad |
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| Rok vydání: | 2011 |
| Předmět: |
Microscopy
Confocal biology Neurodegeneration Microtubule organizing center Vimentin Mice Transgenic Cell Biology medicine.disease Cell biology Cellular and Molecular Neuroscience Amyloid beta-Protein Precursor Mice Aggresome Ubiquitin Proteasome mental disorders Amyloid precursor protein biology.protein Proteasome inhibitor medicine Animals Humans Enzyme Inhibitors Proteasome Inhibitors medicine.drug |
| Zdroj: | Neurochemistry international. 60(5) |
| ISSN: | 1872-9754 |
| Popis: | Aggresomes are cytoplasmic inclusions which are localized at the microtubule organizing center (MTOC) as a result of induced proteasome inhibition, stress or over-expression of certain proteins. Aggresomes are linked to the pathogenesis of many neurodegenerative diseases. Here we studied whether amyloid precursor protein (APP), a type-I transmembrane glycoprotein, is localized in aggresomes after exposure to stress condition. Using confocal microscopy we found that APP is located in aggresomes and co-localized with vimentin, γ-tubulin, 20S and ubiquitin at the MTOC in response to proteasome dysfunction. An interaction between vimentin and APP was found after proteasome inhibition suggesting that APP is an additional protein constituent of aggresomes. Suppression of the proteasome system in APP-HEK293 cells overexpressing APP or transfected with APP Swedish mutation caused an accumulation of stable, detergent-insoluble forms of APP containing poly-ubiquitinated proteins. In addition, brain homogenates from transgenic mice expressing human APP with the Arctic mutation demonstrated an interaction between APP and the aggresomal-marker vimentin. These data suggest that malfunctioning of the proteasome system caused by mutation or overexpression of pathological or non-pathological proteins may lead to the accumulation of stable aggresomes, perhaps contributing to the neurodegeneration. |
| Databáze: | OpenAIRE |
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