Cargando…
Protein Translocation Acquires Substrate Selectivity Through ER Stress-Induced Reassembly of Translocon Auxiliary Components
Protein import across the endoplasmic reticulum membrane is physiologically regulated in a substrate-selective manner to ensure the protection of stressed ER from the overload of misfolded proteins. However, it is poorly understood how different types of substrates are accurately distinguished and d...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072789/ https://www.ncbi.nlm.nih.gov/pubmed/32102453 http://dx.doi.org/10.3390/cells9020518 |
_version_ | 1783506488342347776 |
---|---|
author | Lee, Sohee Shin, Yejin Kim, Kyunggon Song, Youngsup Kim, Yongsub Kang, Sang-Wook |
author_facet | Lee, Sohee Shin, Yejin Kim, Kyunggon Song, Youngsup Kim, Yongsub Kang, Sang-Wook |
author_sort | Lee, Sohee |
collection | PubMed |
description | Protein import across the endoplasmic reticulum membrane is physiologically regulated in a substrate-selective manner to ensure the protection of stressed ER from the overload of misfolded proteins. However, it is poorly understood how different types of substrates are accurately distinguished and disqualified during translocational regulation. In this study, we found poorly assembled translocon-associated protein (TRAP) complexes in stressed ER. Immunoaffinity purification identified calnexin in the TRAP complex in which poor assembly inhibited membrane insertion of the prion protein (PrP) in a transmembrane sequence-selective manner, through translocational regulation. This reaction was induced selectively by redox perturbation, rather than calcium depletion, in the ER. The liberation of ERp57 from calnexin appeared to be the reason for the redox sensitivity. Stress-independent disruption of the TRAP complex prevented a pathogenic transmembrane form of PrP (ctmPrP) from accumulating in the ER. This study uncovered a previously unappreciated role for calnexin in assisting the redox-sensitive function of the TRAP complex and provided insights into the ER stress-induced reassembly of translocon auxiliary components as a key mechanism by which protein translocation acquires substrate selectivity. |
format | Online Article Text |
id | pubmed-7072789 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70727892020-03-19 Protein Translocation Acquires Substrate Selectivity Through ER Stress-Induced Reassembly of Translocon Auxiliary Components Lee, Sohee Shin, Yejin Kim, Kyunggon Song, Youngsup Kim, Yongsub Kang, Sang-Wook Cells Article Protein import across the endoplasmic reticulum membrane is physiologically regulated in a substrate-selective manner to ensure the protection of stressed ER from the overload of misfolded proteins. However, it is poorly understood how different types of substrates are accurately distinguished and disqualified during translocational regulation. In this study, we found poorly assembled translocon-associated protein (TRAP) complexes in stressed ER. Immunoaffinity purification identified calnexin in the TRAP complex in which poor assembly inhibited membrane insertion of the prion protein (PrP) in a transmembrane sequence-selective manner, through translocational regulation. This reaction was induced selectively by redox perturbation, rather than calcium depletion, in the ER. The liberation of ERp57 from calnexin appeared to be the reason for the redox sensitivity. Stress-independent disruption of the TRAP complex prevented a pathogenic transmembrane form of PrP (ctmPrP) from accumulating in the ER. This study uncovered a previously unappreciated role for calnexin in assisting the redox-sensitive function of the TRAP complex and provided insights into the ER stress-induced reassembly of translocon auxiliary components as a key mechanism by which protein translocation acquires substrate selectivity. MDPI 2020-02-24 /pmc/articles/PMC7072789/ /pubmed/32102453 http://dx.doi.org/10.3390/cells9020518 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lee, Sohee Shin, Yejin Kim, Kyunggon Song, Youngsup Kim, Yongsub Kang, Sang-Wook Protein Translocation Acquires Substrate Selectivity Through ER Stress-Induced Reassembly of Translocon Auxiliary Components |
title | Protein Translocation Acquires Substrate Selectivity Through ER Stress-Induced Reassembly of Translocon Auxiliary Components |
title_full | Protein Translocation Acquires Substrate Selectivity Through ER Stress-Induced Reassembly of Translocon Auxiliary Components |
title_fullStr | Protein Translocation Acquires Substrate Selectivity Through ER Stress-Induced Reassembly of Translocon Auxiliary Components |
title_full_unstemmed | Protein Translocation Acquires Substrate Selectivity Through ER Stress-Induced Reassembly of Translocon Auxiliary Components |
title_short | Protein Translocation Acquires Substrate Selectivity Through ER Stress-Induced Reassembly of Translocon Auxiliary Components |
title_sort | protein translocation acquires substrate selectivity through er stress-induced reassembly of translocon auxiliary components |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072789/ https://www.ncbi.nlm.nih.gov/pubmed/32102453 http://dx.doi.org/10.3390/cells9020518 |
work_keys_str_mv | AT leesohee proteintranslocationacquiressubstrateselectivitythrougherstressinducedreassemblyoftransloconauxiliarycomponents AT shinyejin proteintranslocationacquiressubstrateselectivitythrougherstressinducedreassemblyoftransloconauxiliarycomponents AT kimkyunggon proteintranslocationacquiressubstrateselectivitythrougherstressinducedreassemblyoftransloconauxiliarycomponents AT songyoungsup proteintranslocationacquiressubstrateselectivitythrougherstressinducedreassemblyoftransloconauxiliarycomponents AT kimyongsub proteintranslocationacquiressubstrateselectivitythrougherstressinducedreassemblyoftransloconauxiliarycomponents AT kangsangwook proteintranslocationacquiressubstrateselectivitythrougherstressinducedreassemblyoftransloconauxiliarycomponents |