A role of BAG3 in regulating SNCA/α-synuclein clearance via selective macroautophagy

Publication date: December 2017
Source:Neurobiology of Aging, Volume 60
Author(s): Yu-Lan Cao, Ya-Ping Yang, Cheng-Jie Mao, Xiao-Qi Zhang, Chen-Tao Wang, Jing Yang, Dong-Jun Lv, Fen Wang, Li-Fang Hu, Chun-Feng Liu
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.



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