Protein folding state-dependent sorting at the Golgi apparatus

@article{Hellerschmied2019ProteinFS,
  title={Protein folding state-dependent sorting at the Golgi apparatus},
  author={D. Hellerschmied and Yevgeniy V. Serebrenik and L. Shao and George M. Burslem and C. Crews},
  journal={Molecular Biology of the Cell},
  year={2019},
  volume={30},
  pages={2296 - 2308}
}
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… Expand
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References

SHOWING 1-10 OF 66 REFERENCES
Targeted protein unfolding uncovers a Golgi-specific transcriptional stress response
TLDR
The Golgi’s ability to sense misfolded proteins and establish new aspects of Golgi autoregulation are highlighted and previously uncharacterized genes that are essential for Golgi structural integrity are revealed. Expand
Protein folding and modification in the mammalian endoplasmic reticulum.
Analysis of the human genome reveals that approximately a third of all open reading frames code for proteins that enter the endoplasmic reticulum (ER), demonstrating the importance of this organelleExpand
Starvation-Dependent Regulation of Golgi Quality Control Links the TOR Signaling and Vacuolar Protein Sorting Pathways.
TLDR
Early cellular responses to starvation include the targeting of specific Golgi proteins for degradation, a phenomenon reminiscent of the inactivation of BTN1, the yeast Batten disease gene ortholog. Expand
Transmembrane domain quality control systems operate at the endoplasmic reticulum and Golgi apparatus
TLDR
It is found that the three TMDs examined prevent trafficking of CD8 to the cell surface via potentially distinct mechanisms, and preliminary experiments indicate that protein retained by quality control mechanisms at the Golgi are targeted to lysosomes for degradation. Expand
Quality control in the secretory pathway: retention of a misfolded viral membrane glycoprotein involves cycling between the ER, intermediate compartment, and Golgi apparatus
TLDR
The long-term fate of a membrane glycoprotein with a temperature-dependent folding defect, the G protein of tsO45 vesicular stomatitis virus, is monitored, showing that the misfolded G protein is not retained in the ER alone; it can move to the intermediate compartment and to the cis-Golgi network but is then recycled back to the ER. Expand
Retrograde Transport of Golgi-localized Proteins to the ER
TLDR
The attachment of the thermosensitive VSVGtsO45 lumenal domain to proteins promises to be a useful tool for studying the molecular mechanisms and specificity of retrograde traffic to the ER. Expand
ER Stress-Induced Clearance of Misfolded GPI-Anchored Proteins via the Secretory Pathway
TLDR
It is reported that, when ER folding capacity is saturated during stress, misfolded glycosylphosphatidylinositol-anchored proteins dissociate from resident ER chaperones, engage export receptors, and quantitatively leave the ER via vesicular transport to the Golgi. Expand
Routing Misfolded Proteins through the Multivesicular Body (MVB) Pathway Protects against Proteotoxicity*
TLDR
Surprisingly, the transport mode plays a second crucial function in neutralizing potential substrate toxicity and demonstrating a new role of the MVB pathway in protein quality control. Expand
A pH-Regulated Quality Control Cycle for Surveillance of Secretory Protein Assembly
TLDR
How ERp44 cycles between cisGolgi and ER in a pH-regulated manner, patrolling assembly of disulfide-linked oligomers such as IgM and adiponectin is unveiled, couples secretion fidelity and efficiency downstream of the calnexin/calreticulin and BiP-dependent quality control cycles. Expand
Protein quality control at the mitochondrion.
TLDR
The biochemical processes and the enzymatic components that are responsible for maintaining mitochondrial protein homoeostasis, including a mitochondrial unfolded protein response, are summarized. Expand
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4
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