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Induced oligomerization targets Golgi proteins for degradation in lysosomes
Manganese protects cells against forms of Shiga toxin by down-regulating the cycling Golgi protein GPP130. Down-regulation occurs when Mn binding causes GPP130 to oligomerize and traffic to lysosomes. To determine how GPP130 is redirected to lysosomes, we tested the role of GGA1 and clathrin, which...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666137/ https://www.ncbi.nlm.nih.gov/pubmed/26446839 http://dx.doi.org/10.1091/mbc.E15-04-0207 |
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author | Tewari, Ritika Bachert, Collin Linstedt, Adam D. |
author_facet | Tewari, Ritika Bachert, Collin Linstedt, Adam D. |
author_sort | Tewari, Ritika |
collection | PubMed |
description | Manganese protects cells against forms of Shiga toxin by down-regulating the cycling Golgi protein GPP130. Down-regulation occurs when Mn binding causes GPP130 to oligomerize and traffic to lysosomes. To determine how GPP130 is redirected to lysosomes, we tested the role of GGA1 and clathrin, which mediate sorting in the canonical Golgi-to-lysosome pathway. GPP130 oligomerization was induced using either Mn or a self-interacting version of the FKBP domain. Inhibition of GGA1 or clathrin specifically blocked GPP130 redistribution, suggesting recognition of the aggregated GPP130 by the GGA1/clathrin-sorting complex. Unexpectedly, however, GPP130’s cytoplasmic domain was not required, and redistribution also occurred after removal of GPP130 sequences needed for its normal cycling. Therefore, to test whether aggregate recognition might be a general phenomenon rather than one involving a specific GPP130 determinant, we induced homo-oligomerization of two unrelated Golgi-targeted constructs using the FKBP strategy. These were targeted to the cis- and trans-Golgi, respectively, using domains from mannosidase-1 and galactosyltransferase. Significantly, upon oligomerization, each redistributed to peripheral punctae and was degraded. This occurred in the absence of detectable UPR activation. These findings suggest the unexpected presence of quality control in the Golgi that recognizes aggregated Golgi proteins and targets them for degradation in lysosomes. |
format | Online Article Text |
id | pubmed-4666137 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-46661372016-02-16 Induced oligomerization targets Golgi proteins for degradation in lysosomes Tewari, Ritika Bachert, Collin Linstedt, Adam D. Mol Biol Cell Articles Manganese protects cells against forms of Shiga toxin by down-regulating the cycling Golgi protein GPP130. Down-regulation occurs when Mn binding causes GPP130 to oligomerize and traffic to lysosomes. To determine how GPP130 is redirected to lysosomes, we tested the role of GGA1 and clathrin, which mediate sorting in the canonical Golgi-to-lysosome pathway. GPP130 oligomerization was induced using either Mn or a self-interacting version of the FKBP domain. Inhibition of GGA1 or clathrin specifically blocked GPP130 redistribution, suggesting recognition of the aggregated GPP130 by the GGA1/clathrin-sorting complex. Unexpectedly, however, GPP130’s cytoplasmic domain was not required, and redistribution also occurred after removal of GPP130 sequences needed for its normal cycling. Therefore, to test whether aggregate recognition might be a general phenomenon rather than one involving a specific GPP130 determinant, we induced homo-oligomerization of two unrelated Golgi-targeted constructs using the FKBP strategy. These were targeted to the cis- and trans-Golgi, respectively, using domains from mannosidase-1 and galactosyltransferase. Significantly, upon oligomerization, each redistributed to peripheral punctae and was degraded. This occurred in the absence of detectable UPR activation. These findings suggest the unexpected presence of quality control in the Golgi that recognizes aggregated Golgi proteins and targets them for degradation in lysosomes. The American Society for Cell Biology 2015-12-01 /pmc/articles/PMC4666137/ /pubmed/26446839 http://dx.doi.org/10.1091/mbc.E15-04-0207 Text en © 2015 Tewari et al. 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 Tewari, Ritika Bachert, Collin Linstedt, Adam D. Induced oligomerization targets Golgi proteins for degradation in lysosomes |
title | Induced oligomerization targets Golgi proteins for degradation in lysosomes |
title_full | Induced oligomerization targets Golgi proteins for degradation in lysosomes |
title_fullStr | Induced oligomerization targets Golgi proteins for degradation in lysosomes |
title_full_unstemmed | Induced oligomerization targets Golgi proteins for degradation in lysosomes |
title_short | Induced oligomerization targets Golgi proteins for degradation in lysosomes |
title_sort | induced oligomerization targets golgi proteins for degradation in lysosomes |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4666137/ https://www.ncbi.nlm.nih.gov/pubmed/26446839 http://dx.doi.org/10.1091/mbc.E15-04-0207 |
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