| Autor: |
Thomas, Labisch, Stephan, Buchkremer, Vietxuan, Phan, Laxmikanth, Kollipara, Christian, Gatz, Chris, Lentz, Kay, Nolte, Jörg, Vervoorts, José Andrés González, Coraspe, Albert, Sickmann, Stephanie, Carr, René P, Zahedi, Joachim, Weis, Andreas, Roos |
| Rok vydání: |
2016 |
| Předmět: |
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| Zdroj: |
Molecular neurobiology. 55(3) |
| ISSN: |
1559-1182 |
| Popis: |
SIL1 acts as a co-chaperone for the major ER-resident chaperone BiP and thus plays a role in many BiP-dependent cellular functions such as protein-folding control and unfolded protein response. Whereas the increase of BiP upon cellular stress conditions is a well-known phenomenon, elevation of SIL1 under stress conditions was thus far solely studied in yeast, and different studies indicated an adverse effect of SIL1 increase. This is seemingly in contrast with the beneficial effect of SIL1 increase in surviving neurons in neurodegenerative disorders such as amyotrophic lateral sclerosis and Alzheimer's disease. Here, we addressed these controversial findings. Applying cell biological, morphological and biochemical methods, we demonstrated that SIL1 increases in various mammalian cells and neuronal tissues upon cellular stress. Investigation of heterozygous SIL1 mutant cells and tissues supported this finding. Moreover, SIL1 protein was found to be stabilized during ER stress. Increased SIL1 initiates ER stress in a concentration-dependent manner which agrees with the described adverse SIL1 effect. However, our results also suggest that protective levels are achieved by the secretion of excessive SIL1 and GRP170 and that moderately increased SIL1 also ameliorates cellular fitness under stress conditions. Our immunoprecipitation results indicate that SIL1 might act in a BiP-independent manner. Proteomic studies showed that SIL1 elevation alters the expression of proteins including crucial players in neurodegeneration, especially in Alzheimer's disease. This finding agrees with our observation of increased SIL1 immunoreactivity in surviving neurons of Alzheimer's disease autopsy cases and supports the assumption that SIL1 plays a protective role in neurodegenerative disorders. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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