A role of BAG3 in regulating SNCA/α-synuclein clearance via selective macroautophagy
| Autor: | Cheng-Jie Mao, Li-Fang Hu, Jing Yang, Chen-Tao Wang, Yu-Lan Cao, Dong-Jun Lv, Xiao-Qi Zhang, Ya-Ping Yang, Fen Wang, Chun-Feng Liu |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Aging ATG5 Gene Expression Mice Transgenic Biology Protein degradation BAG3 PC12 Cells 03 medical and health sciences Sequestosome 1 Mesencephalon Heat shock protein Sequestosome-1 Protein Autophagy Animals HSP70 Heat-Shock Proteins education Adaptor Proteins Signal Transducing Gene knockdown education.field_of_study General Neuroscience Rats Hsp70 Cell biology 030104 developmental biology alpha-Synuclein Cancer research Neurology (clinical) Geriatrics and Gerontology Apoptosis Regulatory Proteins Developmental Biology |
| Zdroj: | Neurobiology of Aging. 60:104-115 |
| ISSN: | 0197-4580 |
| Popis: | Many studies reveal that BAG3 plays a critical role in the regulation of protein degradation via macroautophagy. However, it remains unknown whether BAG3 affects the quality control of α-synuclein (SNCA), a Parkinson's disease–related protein. In this study, we demonstrated the increases of BAG3 expression in the ventral midbrain of SNCA A53T transgenic mice and also in MG132-treated PC12 cells overexpressing wild-type SNCA ( SNCA WT -PC12). Moreover, we showed that BAG3 overexpression was sufficient to enhance the autophagy activity while knockdown of Bag3 reduced it in SNCA WT -PC12 cells. Immunoprecipitation revealed that BAG3 interacted with heat shock protein 70 and sequestosome 1. The immunostaining also showed the perinuclear accumulation and colocalization of BAG3 with these 2 proteins, as well as with LC3 dots in tyrosine hydroxylase–positive neurons in the midbrain of SNCA A53T mice. BAG3 overexpression was able to modulate SNCA degradation via macroautophagy which was prevented by Atg5 knockdown. Taken together, these results indicate that BAG3 plays a relevant role in regulating SNCA clearance via macroautophagy, and the heat shock protein 70-BAG3-sequestosome 1 complex may be involved in this process. |
| Databáze: | OpenAIRE |
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