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Protein folding state-dependent sorting at the Golgi apparatus
In eukaryotic cells, organelle-specific protein quality control (PQC) is critical for maintaining cellular homeostasis. Despite the Golgi apparatus being the major protein processing and sorting site within the secretory pathway, how it contributes to PQC has remained largely unknown. Using differen...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743468/ https://www.ncbi.nlm.nih.gov/pubmed/31166830 http://dx.doi.org/10.1091/mbc.E19-01-0069 |
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author | Hellerschmied, Doris Serebrenik, Yevgeniy V. Shao, Lin Burslem, George M. Crews, Craig M. |
author_facet | Hellerschmied, Doris Serebrenik, Yevgeniy V. Shao, Lin Burslem, George M. Crews, Craig M. |
author_sort | Hellerschmied, Doris |
collection | PubMed |
description | In eukaryotic cells, organelle-specific protein quality control (PQC) is critical for maintaining cellular homeostasis. Despite the Golgi apparatus being the major protein processing and sorting site within the secretory pathway, how it contributes to PQC has remained largely unknown. Using different chemical biology-based protein unfolding systems, we reveal the segregation of unfolded proteins from folded proteins in the Golgi. Quality control (QC) substrates are subsequently exported in distinct carriers, which likely contain unfolded proteins as well as highly oligomerized cargo that mimic protein aggregates. At an additional sorting step, oligomerized proteins are committed to lysosomal degradation, while unfolded proteins localize to the endoplasmic reticulum (ER) and associate with chaperones. These results highlight the existence of checkpoints at which QC substrates are selected for Golgi export and lysosomal degradation. Our data also suggest that the steady-state ER localization of misfolded proteins, observed for several disease-causing mutants, may have different origins. |
format | Online Article Text |
id | pubmed-6743468 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-67434682019-10-16 Protein folding state-dependent sorting at the Golgi apparatus Hellerschmied, Doris Serebrenik, Yevgeniy V. Shao, Lin Burslem, George M. Crews, Craig M. Mol Biol Cell Articles In eukaryotic cells, organelle-specific protein quality control (PQC) is critical for maintaining cellular homeostasis. Despite the Golgi apparatus being the major protein processing and sorting site within the secretory pathway, how it contributes to PQC has remained largely unknown. Using different chemical biology-based protein unfolding systems, we reveal the segregation of unfolded proteins from folded proteins in the Golgi. Quality control (QC) substrates are subsequently exported in distinct carriers, which likely contain unfolded proteins as well as highly oligomerized cargo that mimic protein aggregates. At an additional sorting step, oligomerized proteins are committed to lysosomal degradation, while unfolded proteins localize to the endoplasmic reticulum (ER) and associate with chaperones. These results highlight the existence of checkpoints at which QC substrates are selected for Golgi export and lysosomal degradation. Our data also suggest that the steady-state ER localization of misfolded proteins, observed for several disease-causing mutants, may have different origins. The American Society for Cell Biology 2019-08-01 /pmc/articles/PMC6743468/ /pubmed/31166830 http://dx.doi.org/10.1091/mbc.E19-01-0069 Text en © 2019 Hellerschmied, Serebrenik, et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 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. |
spellingShingle | Articles Hellerschmied, Doris Serebrenik, Yevgeniy V. Shao, Lin Burslem, George M. Crews, Craig M. Protein folding state-dependent sorting at the Golgi apparatus |
title | Protein folding state-dependent sorting at the Golgi apparatus |
title_full | Protein folding state-dependent sorting at the Golgi apparatus |
title_fullStr | Protein folding state-dependent sorting at the Golgi apparatus |
title_full_unstemmed | Protein folding state-dependent sorting at the Golgi apparatus |
title_short | Protein folding state-dependent sorting at the Golgi apparatus |
title_sort | protein folding state-dependent sorting at the golgi apparatus |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743468/ https://www.ncbi.nlm.nih.gov/pubmed/31166830 http://dx.doi.org/10.1091/mbc.E19-01-0069 |
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