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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...

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Detalles Bibliográficos
Autores principales: Tewari, Ritika, Bachert, Collin, Linstedt, Adam D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
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.
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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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