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Limited ER quality control for GPI-anchored proteins
Endoplasmic reticulum (ER) quality control mechanisms target terminally misfolded proteins for ER-associated degradation (ERAD). Misfolded glycophosphatidylinositol-anchored proteins (GPI-APs) are, however, generally poor ERAD substrates and are targeted mainly to the vacuole/lysosome for degradatio...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915193/ https://www.ncbi.nlm.nih.gov/pubmed/27325793 http://dx.doi.org/10.1083/jcb.201602010 |
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author | Sikorska, Natalia Lemus, Leticia Aguilera-Romero, Auxiliadora Manzano-Lopez, Javier Riezman, Howard Muñiz, Manuel Goder, Veit |
author_facet | Sikorska, Natalia Lemus, Leticia Aguilera-Romero, Auxiliadora Manzano-Lopez, Javier Riezman, Howard Muñiz, Manuel Goder, Veit |
author_sort | Sikorska, Natalia |
collection | PubMed |
description | Endoplasmic reticulum (ER) quality control mechanisms target terminally misfolded proteins for ER-associated degradation (ERAD). Misfolded glycophosphatidylinositol-anchored proteins (GPI-APs) are, however, generally poor ERAD substrates and are targeted mainly to the vacuole/lysosome for degradation, leading to predictions that a GPI anchor sterically obstructs ERAD. Here we analyzed the degradation of the misfolded GPI-AP Gas1* in yeast. We could efficiently route Gas1* to Hrd1-dependent ERAD and provide evidence that it contains a GPI anchor, ruling out that a GPI anchor obstructs ERAD. Instead, we show that the normally decreased susceptibility of Gas1* to ERAD is caused by canonical remodeling of its GPI anchor, which occurs in all GPI-APs and provides a protein-independent ER export signal. Thus, GPI anchor remodeling is independent of protein folding and leads to efficient ER export of even misfolded species. Our data imply that ER quality control is limited for the entire class of GPI-APs, many of them being clinically relevant. |
format | Online Article Text |
id | pubmed-4915193 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-49151932016-12-20 Limited ER quality control for GPI-anchored proteins Sikorska, Natalia Lemus, Leticia Aguilera-Romero, Auxiliadora Manzano-Lopez, Javier Riezman, Howard Muñiz, Manuel Goder, Veit J Cell Biol Research Articles Endoplasmic reticulum (ER) quality control mechanisms target terminally misfolded proteins for ER-associated degradation (ERAD). Misfolded glycophosphatidylinositol-anchored proteins (GPI-APs) are, however, generally poor ERAD substrates and are targeted mainly to the vacuole/lysosome for degradation, leading to predictions that a GPI anchor sterically obstructs ERAD. Here we analyzed the degradation of the misfolded GPI-AP Gas1* in yeast. We could efficiently route Gas1* to Hrd1-dependent ERAD and provide evidence that it contains a GPI anchor, ruling out that a GPI anchor obstructs ERAD. Instead, we show that the normally decreased susceptibility of Gas1* to ERAD is caused by canonical remodeling of its GPI anchor, which occurs in all GPI-APs and provides a protein-independent ER export signal. Thus, GPI anchor remodeling is independent of protein folding and leads to efficient ER export of even misfolded species. Our data imply that ER quality control is limited for the entire class of GPI-APs, many of them being clinically relevant. The Rockefeller University Press 2016-06-20 /pmc/articles/PMC4915193/ /pubmed/27325793 http://dx.doi.org/10.1083/jcb.201602010 Text en © 2016 Sikorska et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Sikorska, Natalia Lemus, Leticia Aguilera-Romero, Auxiliadora Manzano-Lopez, Javier Riezman, Howard Muñiz, Manuel Goder, Veit Limited ER quality control for GPI-anchored proteins |
title | Limited ER quality control for GPI-anchored proteins |
title_full | Limited ER quality control for GPI-anchored proteins |
title_fullStr | Limited ER quality control for GPI-anchored proteins |
title_full_unstemmed | Limited ER quality control for GPI-anchored proteins |
title_short | Limited ER quality control for GPI-anchored proteins |
title_sort | limited er quality control for gpi-anchored proteins |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4915193/ https://www.ncbi.nlm.nih.gov/pubmed/27325793 http://dx.doi.org/10.1083/jcb.201602010 |
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