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WRB is the receptor for TRC40/Asna1-mediated insertion of tail-anchored proteins into the ER membrane
Tail-anchored (TA) proteins are post-translationally targeted to and inserted into the endoplasmic reticulum (ER) membrane through their single C-terminal transmembrane domain. Membrane insertion of TA proteins in mammalian cells is mediated by the ATPase TRC40/Asna1 (Get3 in yeast) and a receptor i...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Company of Biologists
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3115773/ https://www.ncbi.nlm.nih.gov/pubmed/21444755 http://dx.doi.org/10.1242/jcs.084277 |
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author | Vilardi, Fabio Lorenz, Holger Dobberstein, Bernhard |
author_facet | Vilardi, Fabio Lorenz, Holger Dobberstein, Bernhard |
author_sort | Vilardi, Fabio |
collection | PubMed |
description | Tail-anchored (TA) proteins are post-translationally targeted to and inserted into the endoplasmic reticulum (ER) membrane through their single C-terminal transmembrane domain. Membrane insertion of TA proteins in mammalian cells is mediated by the ATPase TRC40/Asna1 (Get3 in yeast) and a receptor in the ER membrane. We have identified tryptophan-rich basic protein (WRB), also known as congenital heart disease protein 5 (CHD5), as the ER membrane receptor for TRC40/Asna1. WRB shows sequence similarity to Get1, a subunit of the membrane receptor complex for yeast Get3. Using biochemical and cell imaging approaches, we demonstrate that WRB is an ER-resident membrane protein that interacts with TRC40/Asna1 and recruits it to the ER membrane. We identify the coiled-coil domain of WRB as the binding site for TRC40/Asna1 and show that a soluble form of the coiled-coil domain interferes with TRC40/Asna1-mediated membrane insertion of TA proteins. The identification of WRB as a component of the TRC (Get) pathway for membrane insertion of TA proteins raises new questions concerning the proposed roles of WRB (CHD5) in congenital heart disease, and heart and eye development. |
format | Online Article Text |
id | pubmed-3115773 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Company of Biologists |
record_format | MEDLINE/PubMed |
spelling | pubmed-31157732011-06-20 WRB is the receptor for TRC40/Asna1-mediated insertion of tail-anchored proteins into the ER membrane Vilardi, Fabio Lorenz, Holger Dobberstein, Bernhard J Cell Sci Research Articles Tail-anchored (TA) proteins are post-translationally targeted to and inserted into the endoplasmic reticulum (ER) membrane through their single C-terminal transmembrane domain. Membrane insertion of TA proteins in mammalian cells is mediated by the ATPase TRC40/Asna1 (Get3 in yeast) and a receptor in the ER membrane. We have identified tryptophan-rich basic protein (WRB), also known as congenital heart disease protein 5 (CHD5), as the ER membrane receptor for TRC40/Asna1. WRB shows sequence similarity to Get1, a subunit of the membrane receptor complex for yeast Get3. Using biochemical and cell imaging approaches, we demonstrate that WRB is an ER-resident membrane protein that interacts with TRC40/Asna1 and recruits it to the ER membrane. We identify the coiled-coil domain of WRB as the binding site for TRC40/Asna1 and show that a soluble form of the coiled-coil domain interferes with TRC40/Asna1-mediated membrane insertion of TA proteins. The identification of WRB as a component of the TRC (Get) pathway for membrane insertion of TA proteins raises new questions concerning the proposed roles of WRB (CHD5) in congenital heart disease, and heart and eye development. Company of Biologists 2011-04-15 /pmc/articles/PMC3115773/ /pubmed/21444755 http://dx.doi.org/10.1242/jcs.084277 Text en © 2011. http://creativecommons.org/licenses/by-nc-sa/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial Share Alike License (http://creativecommons.org/licenses/by-nc-sa/3.0), which permits unrestricted non-commercial use, distribution and reproduction in any medium provided that the original work is properly cited and all further distributions of the work or adaptation are subject to the same Creative Commons License terms. |
spellingShingle | Research Articles Vilardi, Fabio Lorenz, Holger Dobberstein, Bernhard WRB is the receptor for TRC40/Asna1-mediated insertion of tail-anchored proteins into the ER membrane |
title | WRB is the receptor for TRC40/Asna1-mediated insertion of tail-anchored proteins into the ER membrane |
title_full | WRB is the receptor for TRC40/Asna1-mediated insertion of tail-anchored proteins into the ER membrane |
title_fullStr | WRB is the receptor for TRC40/Asna1-mediated insertion of tail-anchored proteins into the ER membrane |
title_full_unstemmed | WRB is the receptor for TRC40/Asna1-mediated insertion of tail-anchored proteins into the ER membrane |
title_short | WRB is the receptor for TRC40/Asna1-mediated insertion of tail-anchored proteins into the ER membrane |
title_sort | wrb is the receptor for trc40/asna1-mediated insertion of tail-anchored proteins into the er membrane |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3115773/ https://www.ncbi.nlm.nih.gov/pubmed/21444755 http://dx.doi.org/10.1242/jcs.084277 |
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