2. Academic Validation
  3. The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy

The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy

  • J Cell Biol. 2017 May 1;216(5):1301-1320. doi: 10.1083/jcb.201608039.
Xuezhao Liu 1 2 3,  Yang Li 1,  Xin Wang 1 2 3,  Ruxiao Xing 1 4,  Kai Liu 1,  Qiwen Gan 1 4,  Changyong Tang 1 4,  Zhiyang Gao 1,  Youli Jian 1,  Shouqing Luo 5,  Weixiang Guo 6,  Chonglin Yang 7 2 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
  • 2 State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming 650091, China.
  • 3 Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming 650091, China.
  • 4 Graduate School, University of Chinese Academy of Sciences, Beijing 100093, China.
  • 5 Peninsula Schools of Medicine and Dentistry, Institute of Translational and Stratified Medicine, Plymouth University, Plymouth PL6 8BU, England, UK.
  • 6 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China wxguo@genetics.ac.cn.
  • 7 State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China clyang@genetics.ac.cn.
PMID: 28404643 DOI: 10.1083/jcb.201608039
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 BEACH (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 BEACH 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 CAMRQ2 syndrome, a WDR81-related developmental disorder.

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