【摘 要】
：
Autophagic clearance of misfolded or aggregated proteins is critical to protein quality control and cellular homeostasis.The underlying mechanism is not wel
【机 构】
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State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Bio
【出 处】
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The 7th International Symposium on Autophagy 2015(第七届自噬国际研讨会
论文部分内容阅读
Autophagic clearance of misfolded or aggregated proteins is critical to protein quality control and cellular homeostasis.The underlying mechanism is not well understood.Here we identify the BEACH-and WD40 repeat-containing protein WDR81 as an essential scaffold for elimination of misfolded/aggregated proteins through autophagy.WDR81 localizes to late endosomes/lysosomes but translocates to ubiquitin (Ub)-positive protein aggregates in response to acute protein misfolding stress.Loss of WDR81 causes elevation in Ub-proteins along with the autophagy receptor p62.WDR81 binds to Ub-proteins by interacting with polyubiquitin under protein misfolding stress.Furthermore, WDR81 interacts with p62 and Beclin 1 through the N-terminus and C-terminal WD40 repeats, respectively, promoting the recruitment of p62 and Beclin 1 to aggregated proteins.In C.elegans, deletion of WDR81 homolog leads to accumulation of p62 bodies and exacerbates neuron loss induced by ectopically expressed α-synuclein.These findings establish WDR81 as an essential scaffold facilitating the assembly of the cargo receptor and autophagy machinery at aggregated proteins for their clearance, providing mechanistic implication of WDR81 in developmental disorders such as CAMRQ2 syndrome.
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