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

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 ub...

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Autores principales: Liu, Xuezhao, Li, Yang, Wang, Xin, Xing, Ruxiao, Liu, Kai, Gan, Qiwen, Tang, Changyong, Gao, Zhiyang, Jian, Youli, Luo, Shouqing, Guo, Weixiang, Yang, Chonglin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412561/
https://www.ncbi.nlm.nih.gov/pubmed/28404643
http://dx.doi.org/10.1083/jcb.201608039
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author Liu, Xuezhao
Li, Yang
Wang, Xin
Xing, Ruxiao
Liu, Kai
Gan, Qiwen
Tang, Changyong
Gao, Zhiyang
Jian, Youli
Luo, Shouqing
Guo, Weixiang
Yang, Chonglin
author_facet Liu, Xuezhao
Li, Yang
Wang, Xin
Xing, Ruxiao
Liu, Kai
Gan, Qiwen
Tang, Changyong
Gao, Zhiyang
Jian, Youli
Luo, Shouqing
Guo, Weixiang
Yang, Chonglin
author_sort Liu, Xuezhao
collection PubMed
description 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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spelling pubmed-54125612017-11-01 The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy Liu, Xuezhao Li, Yang Wang, Xin Xing, Ruxiao Liu, Kai Gan, Qiwen Tang, Changyong Gao, Zhiyang Jian, Youli Luo, Shouqing Guo, Weixiang Yang, Chonglin J Cell Biol Research Articles 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. The Rockefeller University Press 2017-05-01 /pmc/articles/PMC5412561/ /pubmed/28404643 http://dx.doi.org/10.1083/jcb.201608039 Text en © 2017 Liu et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Liu, Xuezhao
Li, Yang
Wang, Xin
Xing, Ruxiao
Liu, Kai
Gan, Qiwen
Tang, Changyong
Gao, Zhiyang
Jian, Youli
Luo, Shouqing
Guo, Weixiang
Yang, Chonglin
The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy
title The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy
title_full The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy
title_fullStr The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy
title_full_unstemmed The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy
title_short The BEACH-containing protein WDR81 coordinates p62 and LC3C to promote aggrephagy
title_sort beach-containing protein wdr81 coordinates p62 and lc3c to promote aggrephagy
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5412561/
https://www.ncbi.nlm.nih.gov/pubmed/28404643
http://dx.doi.org/10.1083/jcb.201608039
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