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Manganese-induced trafficking and turnover of GPP130 is mediated by sortilin
Elevated, nontoxic doses of manganese (Mn) protect against Shiga toxin-1–induced cell death via down-regulation of GPP130, a cycling Golgi membrane protein that serves as an endosome-to-Golgi trafficking receptor for the toxin. Mn binds to GPP130 in the Golgi and causes GPP130 to oligomerize/aggrega...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597328/ https://www.ncbi.nlm.nih.gov/pubmed/28768823 http://dx.doi.org/10.1091/mbc.E17-05-0326 |
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author | Venkat, Swati Linstedt, Adam D. |
author_facet | Venkat, Swati Linstedt, Adam D. |
author_sort | Venkat, Swati |
collection | PubMed |
description | Elevated, nontoxic doses of manganese (Mn) protect against Shiga toxin-1–induced cell death via down-regulation of GPP130, a cycling Golgi membrane protein that serves as an endosome-to-Golgi trafficking receptor for the toxin. Mn binds to GPP130 in the Golgi and causes GPP130 to oligomerize/aggregate, and the complexes are diverted to lysosomes. In fact, based on experiments using the self-interacting FM domain, it appears generally true that aggregation of a Golgi protein leads to its lysosomal degradation. How such oligomers are selectively sorted out of the Golgi is unknown. Here we provide evidence that Mn-induced exit of GPP130 from the trans-Golgi network (TGN) toward lysosomes is mediated by the sorting receptor sortilin interacting with the lumenal stem domain of GPP130. In contrast, FM-induced lysosomal trafficking of the Golgi protein galactosyltransferase was sortilin independent and occurred even in the absence of its native lumenal domain. Thus sortilin-dependent as well as sortilin-independent sorting mechanisms target aggregated Golgi membrane proteins for lysosomal degradation. |
format | Online Article Text |
id | pubmed-5597328 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-55973282017-11-30 Manganese-induced trafficking and turnover of GPP130 is mediated by sortilin Venkat, Swati Linstedt, Adam D. Mol Biol Cell Articles Elevated, nontoxic doses of manganese (Mn) protect against Shiga toxin-1–induced cell death via down-regulation of GPP130, a cycling Golgi membrane protein that serves as an endosome-to-Golgi trafficking receptor for the toxin. Mn binds to GPP130 in the Golgi and causes GPP130 to oligomerize/aggregate, and the complexes are diverted to lysosomes. In fact, based on experiments using the self-interacting FM domain, it appears generally true that aggregation of a Golgi protein leads to its lysosomal degradation. How such oligomers are selectively sorted out of the Golgi is unknown. Here we provide evidence that Mn-induced exit of GPP130 from the trans-Golgi network (TGN) toward lysosomes is mediated by the sorting receptor sortilin interacting with the lumenal stem domain of GPP130. In contrast, FM-induced lysosomal trafficking of the Golgi protein galactosyltransferase was sortilin independent and occurred even in the absence of its native lumenal domain. Thus sortilin-dependent as well as sortilin-independent sorting mechanisms target aggregated Golgi membrane proteins for lysosomal degradation. The American Society for Cell Biology 2017-09-15 /pmc/articles/PMC5597328/ /pubmed/28768823 http://dx.doi.org/10.1091/mbc.E17-05-0326 Text en © 2017 Venkat and Linstedt. 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 for Cell Biology. |
spellingShingle | Articles Venkat, Swati Linstedt, Adam D. Manganese-induced trafficking and turnover of GPP130 is mediated by sortilin |
title | Manganese-induced trafficking and turnover of GPP130 is mediated by sortilin |
title_full | Manganese-induced trafficking and turnover of GPP130 is mediated by sortilin |
title_fullStr | Manganese-induced trafficking and turnover of GPP130 is mediated by sortilin |
title_full_unstemmed | Manganese-induced trafficking and turnover of GPP130 is mediated by sortilin |
title_short | Manganese-induced trafficking and turnover of GPP130 is mediated by sortilin |
title_sort | manganese-induced trafficking and turnover of gpp130 is mediated by sortilin |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5597328/ https://www.ncbi.nlm.nih.gov/pubmed/28768823 http://dx.doi.org/10.1091/mbc.E17-05-0326 |
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