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...

Descripción completa

Detalles Bibliográficos
Autores: Sikorska, Natalia, Lemus Rodríguez,Leticia, Aguilera Romero, María Auxiliadora, Manzano López, Javier, Muñiz Guinea, Manuel, Goder, Veit
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2016
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:idus.us.es:11441/56537
Acceso en línea:http://hdl.handle.net/11441/56537
https://doi.org/10.1083/jcb.201602010
Access Level:acceso abierto
id ES_db173a608dfd3f352e36cf99184b5119
oai_identifier_str oai:idus.us.es:11441/56537
network_acronym_str ES
network_name_str España
repository_id_str
spelling Limited ER quality control for GPI-anchored proteinsSikorska, NataliaLemus Rodríguez,LeticiaAguilera Romero, María AuxiliadoraManzano López, JavierMuñiz Guinea, ManuelGoder, VeitEndoplasmic 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 relevantEspaña, Ministerio de Ciencia e Innovación BFU2014-59309-PEspaña, Ministerio de Ciencia e Innovación BFU2009-07290España, Junta de Andalucía P09-CVI-4503Rockefeller University PressGenéticaBiología Celular2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/11441/56537https://doi.org/10.1083/jcb.201602010reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésJournal of Cell Biology, 213 (6), 693-704. BFU2014-59309-PBFU2009-07290P09-CVI-4503http://dx.doi.org/10.1083/jcb.201602010info:eu-repo/semantics/openAccessoai:idus.us.es:11441/565372026-06-17T12:51:07Z
dc.title.none.fl_str_mv Limited ER quality control for GPI-anchored proteins
title Limited ER quality control for GPI-anchored proteins
spellingShingle Limited ER quality control for GPI-anchored proteins
Sikorska, Natalia
title_short 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_sort Limited ER quality control for GPI-anchored proteins
dc.creator.none.fl_str_mv Sikorska, Natalia
Lemus Rodríguez,Leticia
Aguilera Romero, María Auxiliadora
Manzano López, Javier
Muñiz Guinea, Manuel
Goder, Veit
author Sikorska, Natalia
author_facet Sikorska, Natalia
Lemus Rodríguez,Leticia
Aguilera Romero, María Auxiliadora
Manzano López, Javier
Muñiz Guinea, Manuel
Goder, Veit
author_role author
author2 Lemus Rodríguez,Leticia
Aguilera Romero, María Auxiliadora
Manzano López, Javier
Muñiz Guinea, Manuel
Goder, Veit
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Genética
Biología Celular
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
publishDate 2016
dc.date.none.fl_str_mv 2016
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11441/56537
https://doi.org/10.1083/jcb.201602010
url http://hdl.handle.net/11441/56537
https://doi.org/10.1083/jcb.201602010
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Journal of Cell Biology, 213 (6), 693-704.
BFU2014-59309-P
BFU2009-07290
P09-CVI-4503
http://dx.doi.org/10.1083/jcb.201602010
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Rockefeller University Press
publisher.none.fl_str_mv Rockefeller University Press
dc.source.none.fl_str_mv reponame:idUS. Depósito de Investigación de la Universidad de Sevilla
instname:Universidad de Sevilla (US)
instname_str Universidad de Sevilla (US)
reponame_str idUS. Depósito de Investigación de la Universidad de Sevilla
collection idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869421642089758720
score 15.301603

Similares en LA Referencia