ArticleGenetics2012
The endosomal protein-sorting receptor sortilin has a role in trafficking α-1 antitrypsin.
Article in Genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 48 citations in OpenAlex.
- Mechanisms of Quality Control in GPI-Anchored Proteins: The Central Role of the Lipid Anchor.International journal of molecular sciences · 2026Review
- Endoplasmic reticulum and Golgi stress signaling-mediated regulation of protein secretion.Cellular & molecular biology letters · 2026Review
- Identification of polycystin 2 missense mutants targeted for endoplasmic reticulum-associated degradation.American journal of physiology. Cell physiology · 2025Article
- Isoform-dependent lysosomal degradation and internalization of apolipoprotein E requires autophagy proteins.Journal of cell science · 2022Article
- The Autophagy Pathway: A Critical Route in the Disposal of Alpha 1-Antitrypsin Aggregates That Holds Many Mysteries.International journal of molecular sciences · 2021Review
- ER Disposal Pathways in Chronic Liver Disease: Protective, Pathogenic, and Potential Therapeutic Targets.Frontiers in molecular biosciences · 2021Review
- Upregulation of Sortilin, a Lysosomal Sorting Receptor, Corresponds with Reduced Bioavailability of Latent TGFβ in Mucolipidosis II Cells.Biomolecules · 2020Article
- Protein folding state-dependent sorting at the Golgi apparatus.Molecular biology of the cell · 2019Article
- A COPII subunit acts with an autophagy receptor to target endoplasmic reticulum for degradation.Science (New York, N.Y.) · 2019Article
- ER-to-lysosome-associated degradation of proteasome-resistant ATZ polymers occurs via receptor-mediated vesicular transport.The EMBO journal · 2018Article
- Endoplasmic reticulum turnover: ER-phagy and other flavors in selective and non-selective ER clearance.F1000Research · 2018Review
- Neurodegeneration-associated mutant TREM2 proteins abortively cycle between the ER and ER-Golgi intermediate compartment.Molecular biology of the cell · 2017Article
- Early-onset torsion dystonia: a novel high-throughput yeast genetic screen for factors modifying protein levels of torsinAΔE.Disease models & mechanisms · 2017Article
- Endoplasmic reticulum-associated degradation of the renal potassium channel, ROMK, leads to type II Bartter syndrome.The Journal of biological chemistry · 2017Article
- Sortilin Fragments Deposit at Senile Plaques in Human Cerebrum.Frontiers in neuroanatomy · 2017Article
- ERAD defects and the HFE-H63D variant are associated with increased risk of liver damages in Alpha 1-Antitrypsin Deficiency.PloS one · 2017Article
- α1-antitrypsin Deficiency: A Misfolded Secretory Protein Variant with Unique Effects on the Endoplasmic Reticulum.Endoplasmic reticulum stress in diseases · 2016Article
- FBG1 Is the Final Arbitrator of A1AT-Z Degradation.PloS one · 2015Article
- Energy landscapes of functional proteins are inherently risky.Nature chemical biology · 2014Article
- Sortilin and lipoprotein metabolism: making sense out of complexity.Current opinion in lipidology · 2014Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Up to 1 in 3000 individuals in the United States have α-1 antitrypsin deficiency, and the most common cause of this disease is homozygosity for the antitrypsin-Z variant (ATZ). ATZ is inefficiently secreted, resulting in protein deficiency in the lungs and toxic polymer accumulation in the liver. However, only a subset of patients suffer from liver disease, suggesting that genetic factors predispose individuals to liver disease. To identify candidate factors, we developed a yeast ATZ expression system that recapitulates key features of the disease-causing protein. We then adapted this system to screen the yeast deletion mutant collection to identify conserved genes that affect ATZ secretion and thus may modify the risk for developing liver disease. The results of the screen and associated assays indicate that ATZ is degraded in the vacuole after being routed from the Golgi. In fact, one of the strongest hits from our screen was Vps10, which can serve as a receptor for the delivery of aberrant proteins to the vacuole. Because genome-wide association studies implicate the human Vps10 homolog, sortilin, in cardiovascular disease, and because hepatic cell lines that stably express wild-type or mutant sortilin were recently established, we examined whether ATZ levels and secretion are affected by sortilin. As hypothesized, sortilin function impacts the levels of secreted ATZ in mammalian cells. This study represents the first genome-wide screen for factors that modulate ATZ secretion and has led to the identification of a gene that may modify disease severity or presentation in individuals with ATZ-associated liver disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.