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Mol Biol Cell. 2019 Aug 1;30(17):2296-2308. doi: 10.1091/mbc.E19-01-0069. Epub 2019 Jun 5.

Protein folding state-dependent sorting at the Golgi apparatus.

Author information

1
Department of Molecular, Cellular and Developmental Biology.
2
Department of Neuroscience, Yale School of Medicine, New Haven, CT 06520.
3
Department of Chemistry, Yale University, New Haven, CT 06511.
4
Department of Pharmacology, Yale University, New Haven, CT 06511.

Abstract

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.

PMID:
31166830
DOI:
10.1091/mbc.E19-01-0069

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