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TANGO1 and SEC12 are copackaged with procollagen I to facilitate the generation of large COPII carriers
Large coat protein complex II (COPII)-coated vesicles serve to convey the large cargo procollagen I (PC1) from the endoplasmic reticulum (ER). The link between large cargo in the lumen of the ER and modulation of the COPII machinery remains unresolved. TANGO1 is required for PC secretion and interac...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
National Academy of Sciences
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310809/ https://www.ncbi.nlm.nih.gov/pubmed/30545919 http://dx.doi.org/10.1073/pnas.1814810115 |
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author | Yuan, Lin Kenny, Samuel J. Hemmati, Juliet Xu, Ke Schekman, Randy |
author_facet | Yuan, Lin Kenny, Samuel J. Hemmati, Juliet Xu, Ke Schekman, Randy |
author_sort | Yuan, Lin |
collection | PubMed |
description | Large coat protein complex II (COPII)-coated vesicles serve to convey the large cargo procollagen I (PC1) from the endoplasmic reticulum (ER). The link between large cargo in the lumen of the ER and modulation of the COPII machinery remains unresolved. TANGO1 is required for PC secretion and interacts with PC and COPII on opposite sides of the ER membrane, but evidence suggests that TANGO1 is retained in the ER, and not included in normal size (<100 nm) COPII vesicles. Here we show that TANGO1 is exported out of the ER in large COPII-coated PC1 carriers, and retrieved back to the ER by the retrograde coat, COPI, mediated by the C-terminal RDEL retrieval sequence of HSP47. TANGO1 is known to target the COPII initiation factor SEC12 to ER exit sites through an interacting protein, cTAGE5. SEC12 is important for the growth of COPII vesicles, but it is not sorted into small budded vesicles. We found both cTAGE5 and SEC12 were exported with TANGO1 in large COPII carriers. In contrast to its exclusion from small transport vesicles, SEC12 was particularly enriched around ER membranes and large COPII carriers that contained PC1. We constructed a split GFP system to recapitulate the targeting of SEC12 to PC1 via the luminal domain of TANGO1. The minimal targeting system enriched SEC12 around PC1 and generated large PC1 carriers. We conclude that TANGO1, cTAGE5, and SEC12 are copacked with PC1 into COPII carriers to increase the size of COPII, thus ensuring the capture of large cargo. |
format | Online Article Text |
id | pubmed-6310809 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | National Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-63108092019-01-04 TANGO1 and SEC12 are copackaged with procollagen I to facilitate the generation of large COPII carriers Yuan, Lin Kenny, Samuel J. Hemmati, Juliet Xu, Ke Schekman, Randy Proc Natl Acad Sci U S A PNAS Plus Large coat protein complex II (COPII)-coated vesicles serve to convey the large cargo procollagen I (PC1) from the endoplasmic reticulum (ER). The link between large cargo in the lumen of the ER and modulation of the COPII machinery remains unresolved. TANGO1 is required for PC secretion and interacts with PC and COPII on opposite sides of the ER membrane, but evidence suggests that TANGO1 is retained in the ER, and not included in normal size (<100 nm) COPII vesicles. Here we show that TANGO1 is exported out of the ER in large COPII-coated PC1 carriers, and retrieved back to the ER by the retrograde coat, COPI, mediated by the C-terminal RDEL retrieval sequence of HSP47. TANGO1 is known to target the COPII initiation factor SEC12 to ER exit sites through an interacting protein, cTAGE5. SEC12 is important for the growth of COPII vesicles, but it is not sorted into small budded vesicles. We found both cTAGE5 and SEC12 were exported with TANGO1 in large COPII carriers. In contrast to its exclusion from small transport vesicles, SEC12 was particularly enriched around ER membranes and large COPII carriers that contained PC1. We constructed a split GFP system to recapitulate the targeting of SEC12 to PC1 via the luminal domain of TANGO1. The minimal targeting system enriched SEC12 around PC1 and generated large PC1 carriers. We conclude that TANGO1, cTAGE5, and SEC12 are copacked with PC1 into COPII carriers to increase the size of COPII, thus ensuring the capture of large cargo. National Academy of Sciences 2018-12-26 2018-12-13 /pmc/articles/PMC6310809/ /pubmed/30545919 http://dx.doi.org/10.1073/pnas.1814810115 Text en Copyright © 2018 the Author(s). Published by PNAS. http://creativecommons.org/licenses/by/4.0/ This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | PNAS Plus Yuan, Lin Kenny, Samuel J. Hemmati, Juliet Xu, Ke Schekman, Randy TANGO1 and SEC12 are copackaged with procollagen I to facilitate the generation of large COPII carriers |
title | TANGO1 and SEC12 are copackaged with procollagen I to facilitate the generation of large COPII carriers |
title_full | TANGO1 and SEC12 are copackaged with procollagen I to facilitate the generation of large COPII carriers |
title_fullStr | TANGO1 and SEC12 are copackaged with procollagen I to facilitate the generation of large COPII carriers |
title_full_unstemmed | TANGO1 and SEC12 are copackaged with procollagen I to facilitate the generation of large COPII carriers |
title_short | TANGO1 and SEC12 are copackaged with procollagen I to facilitate the generation of large COPII carriers |
title_sort | tango1 and sec12 are copackaged with procollagen i to facilitate the generation of large copii carriers |
topic | PNAS Plus |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310809/ https://www.ncbi.nlm.nih.gov/pubmed/30545919 http://dx.doi.org/10.1073/pnas.1814810115 |
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