Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Venkat, Swati, Linstedt, Adam D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
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
_version_ 1783263690679648256
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
work_keys_str_mv AT venkatswati manganeseinducedtraffickingandturnoverofgpp130ismediatedbysortilin
AT linstedtadamd manganeseinducedtraffickingandturnoverofgpp130ismediatedbysortilin