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The BEACH-containing Protein WDR81 Coordinates p62 and LC3C to Promote Aggrephagy
Xuezhao Liu, Yang Li, Xin Wang, Ruxiao Xing, Kai Liu, Qiwen Gan, Changyong Tang, Zhiyang Gao, Youli Jian, Shouqing Luo, Weixiang Guo, and Chonglin Yang
The Journal of Cell Biology
Abstract
Autophagy-dependent clearance of ubiquitinated and aggregated proteins is critical to protein quality control, but the underlying mechanisms are not well understood. Here, we report the essential role of the BEA CH (beige and Chediak–Higashi) and WD40 repeat-containing protein WDR81 in eliminating ubiquitinated proteins through autophagy. WDR81 associates with ubiquitin (Ub)-positive protein foci, and its loss causes accumulation of Ub proteins and the autophagy cargo receptor p62. WDR81 interacts with p62, facilitating recognition of Ub proteins by p62. Furthermore, WDR81 interacts with LC3C through canonical LC3-interacting regions in the BEA CH domain, promoting LC3C recruitment to ubiquitinated proteins. Inactivation of LC3C or defective autophagy results in accumulation of Ub protein aggregates enriched for WDR81. In mice, WDR81 inactivation causes accumulation of p62 bodies in cortical and striatal neurons in the brain. These data suggest that WDR81 coordinates p62 and LC3C to facilitate autophagic removal of Ub proteins, and provide important insights into CAM RQ2 syndrome, a WDR81-related developmental disorder.
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论文编号: |
DOI:10.1083/jcb.201608039 |
论文题目: |
The BEACH-containing Protein WDR81 Coordinates p62 and LC3C to Promote Aggrephagy |
英文论文题目: |
The BEACH-containing Protein WDR81 Coordinates p62 and LC3C to Promote Aggrephagy |
第一作者: |
Xuezhao Liu, Yang Li, Xin Wang, Ruxiao Xing, Kai Liu, Qiwen Gan, Changyong Tang, Zhiyang Gao, Youli Jian, Shouqing Luo, Weixiang Guo, and Chonglin Yang |
英文第一作者: |
Xuezhao Liu, Yang Li, Xin Wang, Ruxiao Xing, Kai Liu, Qiwen Gan, Changyong Tang, Zhiyang Gao, Youli Jian, Shouqing Luo, Weixiang Guo, and Chonglin Yang |
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2017-04-14 |
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摘要: |
Autophagy-dependent clearance of ubiquitinated and aggregated proteins is critical to protein quality control, but the underlying mechanisms are not well understood. Here, we report the essential role of the BEA CH (beige and Chediak–Higashi) and WD40 repeat-containing protein WDR81 in eliminating ubiquitinated proteins through autophagy. WDR81 associates with ubiquitin (Ub)-positive protein foci, and its loss causes accumulation of Ub proteins and the autophagy cargo receptor p62. WDR81 interacts with p62, facilitating recognition of Ub proteins by p62. Furthermore, WDR81 interacts with LC3C through canonical LC3-interacting regions in the BEA CH domain, promoting LC3C recruitment to ubiquitinated proteins. Inactivation of LC3C or defective autophagy results in accumulation of Ub protein aggregates enriched for WDR81. In mice, WDR81 inactivation causes accumulation of p62 bodies in cortical and striatal neurons in the brain. These data suggest that WDR81 coordinates p62 and LC3C to facilitate autophagic removal of Ub proteins, and provide important insights into CAM RQ2 syndrome, a WDR81-related developmental disorder. |
英文摘要: |
Autophagy-dependent clearance of ubiquitinated and aggregated proteins is critical to protein quality control, but the underlying mechanisms are not well understood. Here, we report the essential role of the BEA CH (beige and Chediak–Higashi) and WD40 repeat-containing protein WDR81 in eliminating ubiquitinated proteins through autophagy. WDR81 associates with ubiquitin (Ub)-positive protein foci, and its loss causes accumulation of Ub proteins and the autophagy cargo receptor p62. WDR81 interacts with p62, facilitating recognition of Ub proteins by p62. Furthermore, WDR81 interacts with LC3C through canonical LC3-interacting regions in the BEA CH domain, promoting LC3C recruitment to ubiquitinated proteins. Inactivation of LC3C or defective autophagy results in accumulation of Ub protein aggregates enriched for WDR81. In mice, WDR81 inactivation causes accumulation of p62 bodies in cortical and striatal neurons in the brain. These data suggest that WDR81 coordinates p62 and LC3C to facilitate autophagic removal of Ub proteins, and provide important insights into CAM RQ2 syndrome, a WDR81-related developmental disorder. |
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The Journal of Cell Biology |
英文刊物名称: |
The Journal of Cell Biology |
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其它备注: |
Xuezhao Liu, Yang Li, Xin Wang, Ruxiao Xing, Kai Liu, Qiwen Gan, Changyong Tang, Zhiyang Gao, Youli Jian, Shouqing Luo, Weixiang Guo, and Chonglin Yang. The BEACH-containing Protein WDR81 Coordinates p62 and LC3C to Promote Aggrephagy. The Journal of Cell Biology. DOI: 10.1083/jcb.201608039 |
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