ArticleThe American journal of pathology2006
Mutant fibrinogen cleared from the endoplasmic reticulum via endoplasmic reticulum-associated protein degradation and autophagy: an explanation for liver disease.
Article in The American journal of pathology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 101 citations in OpenAlex.
- Regulation of hepatic inclusions and fibrinogen biogenesis by SEL1L-HRD1 ERAD.Nature communications · 2024Article
- PLEKHM2 Loss of Function Impairs the Activity of iPSC-Derived Neurons via Regulation of Autophagic Flux.International journal of molecular sciences · 2022Article
- Rhomboid protease RHBDL4 promotes retrotranslocation of aggregation-prone proteins for degradation.Cell reports · 2022Article
- ER-phagy: mechanisms, regulation, and diseases connected to the lysosomal clearance of the endoplasmic reticulum.Physiological reviews · 2022Review
- Review
- Novel variant fibrinogen γp.C352R produced hypodysfibrinogenemia leading to a bleeding episode and failure of infertility treatment.International journal of hematology · 2021Article
- The Recruitment-Secretory Block ("R-SB") Phenomenon and Endoplasmic Reticulum Storage Diseases.International journal of molecular sciences · 2021Review
- Structural Characteristics in the γ Chain Variants Associated with Fibrinogen Storage Disease Suggest the Underlying Pathogenic Mechanism.International journal of molecular sciences · 2020Article
- Hepatic fibrinogen storage disease and hypofibrinogenemia caused by fibrinogen Aguadilla mutation: a case report.The Journal of international medical research · 2020Article
- Chaperoning Endoplasmic Reticulum-Associated Degradation (ERAD) and Protein Conformational Diseases.Cold Spring Harbor perspectives in biology · 2019Review
- Regulation of the homeostasis of hepatic endoplasmic reticulum and cytochrome P450 enzymes by autophagy.Liver research (Beijing, China) · 2018Article
- Fibrinogen Gamma Chain Mutations Provoke Fibrinogen and Apolipoprotein B Plasma Deficiency and Liver Storage.International journal of molecular sciences · 2017Article
- α1-antitrypsin Deficiency: A Misfolded Secretory Protein Variant with Unique Effects on the Endoplasmic Reticulum.Endoplasmic reticulum stress in diseases · 2016Article
- Autophagy is dispensable to overcome ER stress in the filamentous fungus Aspergillus niger.MicrobiologyOpen · 2016Article
- Mechanism and Regulation of Autophagy and Its Role in Neuronal Diseases.Molecular neurobiology · 2015Review
- Glycoprotein folding and quality-control mechanisms in protein-folding diseases.Disease models & mechanisms · 2014Review
- Autophagy in hepatic fibrosis.BioMed research international · 2014Review
- Capitalizing on the autophagic response for treatment of liver disease caused by alpha-1-antitrypsin deficiency and other genetic diseases.BioMed research international · 2014Review
- Functions of autophagy in normal and diseased liver.Autophagy · 2013Review
- Endoplasmic reticulum and the unfolded protein response: dynamics and metabolic integration.International review of cell and molecular biology · 2013Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The endoplasmic reticulum (ER) quality control processes recognize and remove aberrant proteins from the secretory pathway. Several variants of the plasma protein fibrinogen are recognized as aberrant and degraded by ER-associated protein degradation (ERAD), thus leading to hypofibrinogenemia. A subset of patients with hypofibrinogenemia exhibit hepatic ER accumulation of the variant fibrinogens and develop liver cirrhosis. One such variant named Aguadilla has a substitution of Arg375 to Trp in the gamma-chain. To understand the cellular mechanisms behind clearance of the aberrant Aguadilla gamma-chain, we expressed the mutant gammaD domain in yeast and found that it was cleared from the ER via ERAD. In addition, we discovered that when ERAD was saturated, aggregated Aguadilla gammaD accumulated within the ER while a soluble form of the polypeptide transited the secretory pathway to the trans-Golgi network where it was targeted to the vacuole for degradation. Examination of Aguadilla gammaD in an autophagy-deficient yeast strain showed stabilization of the aggregated ER form, indicating that these aggregates are normally cleared from the ER via the autophagic pathway. These findings have clinical relevance in the understanding of and treatment for ER storage diseases.
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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.