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.
journal_name
Mol Biol Celljournal_title
Molecular biology of the cellauthors
Hellerschmied D,Serebrenik YV,Shao L,Burslem GM,Crews CMdoi
10.1091/mbc.E19-01-0069subject
Has Abstractpub_date
2019-08-01 00:00:00pages
2296-2308issue
17eissn
1059-1524issn
1939-4586journal_volume
30pub_type
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