A conserved ubiquitin- and ESCRT-dependent pathway internalizes human lysosomal membrane proteins for degradation.

The lysosome is an essential organelle to recycle cellular materials and maintain nutrient homeostasis, but the mechanism to down-regulate its membrane proteins is poorly understood. In this study, we performed a cycloheximide (CHX) chase assay to measure the half-lives of approximately 30 human lys...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Weichao Zhang, Xi Yang, Liang Chen, Yun-Yu Liu, Varsha Venkatarangan, Lucas Reist, Phyllis Hanson, Haoxing Xu, Yanzhuang Wang, Ming Li
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/699397cb726c4b3abaae577c9e3fa2c9
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:699397cb726c4b3abaae577c9e3fa2c9
record_format	dspace
spelling	oai:doaj.org-article:699397cb726c4b3abaae577c9e3fa2c92021-12-02T19:54:22ZA conserved ubiquitin- and ESCRT-dependent pathway internalizes human lysosomal membrane proteins for degradation.1544-91731545-788510.1371/journal.pbio.3001361https://doaj.org/article/699397cb726c4b3abaae577c9e3fa2c92021-07-01T00:00:00Zhttps://doi.org/10.1371/journal.pbio.3001361https://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885The lysosome is an essential organelle to recycle cellular materials and maintain nutrient homeostasis, but the mechanism to down-regulate its membrane proteins is poorly understood. In this study, we performed a cycloheximide (CHX) chase assay to measure the half-lives of approximately 30 human lysosomal membrane proteins (LMPs) and identified RNF152 and LAPTM4A as short-lived membrane proteins. The degradation of both proteins is ubiquitin dependent. RNF152 is a transmembrane E3 ligase that ubiquitinates itself, whereas LAPTM4A uses its carboxyl-terminal PY motifs to recruit NEDD4-1 for ubiquitination. After ubiquitination, they are internalized into the lysosome lumen by the endosomal sorting complexes required for transport (ESCRT) machinery for degradation. Strikingly, when ectopically expressed in budding yeast, human RNF152 is still degraded by the vacuole (yeast lysosome) in an ESCRT-dependent manner. Thus, our study uncovered a conserved mechanism to down-regulate lysosome membrane proteins.Weichao ZhangXi YangLiang ChenYun-Yu LiuVarsha VenkataranganLucas ReistPhyllis HansonHaoxing XuYanzhuang WangMing LiPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 19, Iss 7, p e3001361 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Weichao Zhang Xi Yang Liang Chen Yun-Yu Liu Varsha Venkatarangan Lucas Reist Phyllis Hanson Haoxing Xu Yanzhuang Wang Ming Li A conserved ubiquitin- and ESCRT-dependent pathway internalizes human lysosomal membrane proteins for degradation.
description	The lysosome is an essential organelle to recycle cellular materials and maintain nutrient homeostasis, but the mechanism to down-regulate its membrane proteins is poorly understood. In this study, we performed a cycloheximide (CHX) chase assay to measure the half-lives of approximately 30 human lysosomal membrane proteins (LMPs) and identified RNF152 and LAPTM4A as short-lived membrane proteins. The degradation of both proteins is ubiquitin dependent. RNF152 is a transmembrane E3 ligase that ubiquitinates itself, whereas LAPTM4A uses its carboxyl-terminal PY motifs to recruit NEDD4-1 for ubiquitination. After ubiquitination, they are internalized into the lysosome lumen by the endosomal sorting complexes required for transport (ESCRT) machinery for degradation. Strikingly, when ectopically expressed in budding yeast, human RNF152 is still degraded by the vacuole (yeast lysosome) in an ESCRT-dependent manner. Thus, our study uncovered a conserved mechanism to down-regulate lysosome membrane proteins.
format	article
author	Weichao Zhang Xi Yang Liang Chen Yun-Yu Liu Varsha Venkatarangan Lucas Reist Phyllis Hanson Haoxing Xu Yanzhuang Wang Ming Li
author_facet	Weichao Zhang Xi Yang Liang Chen Yun-Yu Liu Varsha Venkatarangan Lucas Reist Phyllis Hanson Haoxing Xu Yanzhuang Wang Ming Li
author_sort	Weichao Zhang
title	A conserved ubiquitin- and ESCRT-dependent pathway internalizes human lysosomal membrane proteins for degradation.
title_short	A conserved ubiquitin- and ESCRT-dependent pathway internalizes human lysosomal membrane proteins for degradation.
title_full	A conserved ubiquitin- and ESCRT-dependent pathway internalizes human lysosomal membrane proteins for degradation.
title_fullStr	A conserved ubiquitin- and ESCRT-dependent pathway internalizes human lysosomal membrane proteins for degradation.
title_full_unstemmed	A conserved ubiquitin- and ESCRT-dependent pathway internalizes human lysosomal membrane proteins for degradation.
title_sort	conserved ubiquitin- and escrt-dependent pathway internalizes human lysosomal membrane proteins for degradation.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/699397cb726c4b3abaae577c9e3fa2c9
work_keys_str_mv	AT weichaozhang aconservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation AT xiyang aconservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation AT liangchen aconservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation AT yunyuliu aconservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation AT varshavenkatarangan aconservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation AT lucasreist aconservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation AT phyllishanson aconservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation AT haoxingxu aconservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation AT yanzhuangwang aconservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation AT mingli aconservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation AT weichaozhang conservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation AT xiyang conservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation AT liangchen conservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation AT yunyuliu conservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation AT varshavenkatarangan conservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation AT lucasreist conservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation AT phyllishanson conservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation AT haoxingxu conservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation AT yanzhuangwang conservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation AT mingli conservedubiquitinandescrtdependentpathwayinternalizeshumanlysosomalmembraneproteinsfordegradation
_version_	1718375903951585280

A conserved ubiquitin- and ESCRT-dependent pathway internalizes human lysosomal membrane proteins for degradation.

Ejemplares similares