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COPII machinery cooperates with ER-localized Hsp40 to sequester misfolded membrane proteins into ER-associated compartments

Proteins that fail to fold in the endoplasmic reticulum (ER) are subjected to ER-associated degradation (ERAD). Certain transmembrane ERAD substrates are segregated into specialized ER subdomains, termed ER-associated compartments (ERACs), before targeting to ubiquitin–proteasome degradation. The tr...

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Autores principales: Kakoi, Shogo, Yorimitsu, Tomohiro, Sato, Ken
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583666/
https://www.ncbi.nlm.nih.gov/pubmed/23303252
http://dx.doi.org/10.1091/mbc.E12-08-0639
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author Kakoi, Shogo
Yorimitsu, Tomohiro
Sato, Ken
author_facet Kakoi, Shogo
Yorimitsu, Tomohiro
Sato, Ken
author_sort Kakoi, Shogo
collection PubMed
description Proteins that fail to fold in the endoplasmic reticulum (ER) are subjected to ER-associated degradation (ERAD). Certain transmembrane ERAD substrates are segregated into specialized ER subdomains, termed ER-associated compartments (ERACs), before targeting to ubiquitin–proteasome degradation. The traffic-independent function of several proteins involved in COPII-mediated ER-to-Golgi transport have been implicated in the segregation of exogenously expressed human cystic fibrosis transmembrane conductance regulator (CFTR) into ERACs in Saccharomyces cerevisiae. Here we focus on the properties of COPII components in the sequestration of enhanced green fluorescent protein (EGFP)–CFTR into ERACs. It has been demonstrated that the temperature-sensitive growth defects in many COPII mutants can be suppressed by overexpressing other genes involved in COPII vesicle formation. However, we show that these suppression abilities are not always correlated with the ability to rescue the ERAC formation defect, suggesting that COPII-mediated EGFP-CFTR entry into ERACs is independent of its ER-to-Golgi trafficking function. In addition to COPII machinery, we find that ER-associated Hsp40s are also involved in the sequestration process by directly interacting with EGFP-CFTR. COPII components and ER-associated Hsp40, Hlj1p, act in the same pathway to sequester EGFP-CFTR into ERACs. Our findings point to an as-yet-undefined role of COPII proteins in the formation of ERACs.
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spelling pubmed-35836662013-05-16 COPII machinery cooperates with ER-localized Hsp40 to sequester misfolded membrane proteins into ER-associated compartments Kakoi, Shogo Yorimitsu, Tomohiro Sato, Ken Mol Biol Cell Articles Proteins that fail to fold in the endoplasmic reticulum (ER) are subjected to ER-associated degradation (ERAD). Certain transmembrane ERAD substrates are segregated into specialized ER subdomains, termed ER-associated compartments (ERACs), before targeting to ubiquitin–proteasome degradation. The traffic-independent function of several proteins involved in COPII-mediated ER-to-Golgi transport have been implicated in the segregation of exogenously expressed human cystic fibrosis transmembrane conductance regulator (CFTR) into ERACs in Saccharomyces cerevisiae. Here we focus on the properties of COPII components in the sequestration of enhanced green fluorescent protein (EGFP)–CFTR into ERACs. It has been demonstrated that the temperature-sensitive growth defects in many COPII mutants can be suppressed by overexpressing other genes involved in COPII vesicle formation. However, we show that these suppression abilities are not always correlated with the ability to rescue the ERAC formation defect, suggesting that COPII-mediated EGFP-CFTR entry into ERACs is independent of its ER-to-Golgi trafficking function. In addition to COPII machinery, we find that ER-associated Hsp40s are also involved in the sequestration process by directly interacting with EGFP-CFTR. COPII components and ER-associated Hsp40, Hlj1p, act in the same pathway to sequester EGFP-CFTR into ERACs. Our findings point to an as-yet-undefined role of COPII proteins in the formation of ERACs. The American Society for Cell Biology 2013-03-01 /pmc/articles/PMC3583666/ /pubmed/23303252 http://dx.doi.org/10.1091/mbc.E12-08-0639 Text en © 2013 Kakoi et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Kakoi, Shogo
Yorimitsu, Tomohiro
Sato, Ken
COPII machinery cooperates with ER-localized Hsp40 to sequester misfolded membrane proteins into ER-associated compartments
title COPII machinery cooperates with ER-localized Hsp40 to sequester misfolded membrane proteins into ER-associated compartments
title_full COPII machinery cooperates with ER-localized Hsp40 to sequester misfolded membrane proteins into ER-associated compartments
title_fullStr COPII machinery cooperates with ER-localized Hsp40 to sequester misfolded membrane proteins into ER-associated compartments
title_full_unstemmed COPII machinery cooperates with ER-localized Hsp40 to sequester misfolded membrane proteins into ER-associated compartments
title_short COPII machinery cooperates with ER-localized Hsp40 to sequester misfolded membrane proteins into ER-associated compartments
title_sort copii machinery cooperates with er-localized hsp40 to sequester misfolded membrane proteins into er-associated compartments
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583666/
https://www.ncbi.nlm.nih.gov/pubmed/23303252
http://dx.doi.org/10.1091/mbc.E12-08-0639
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