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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...

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Autores principales: Hellerschmied, Doris, Serebrenik, Yevgeniy V., Shao, Lin, Burslem, George M., Crews, Craig M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2019
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.
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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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