ArticleScientific reports2015
Downregulation of the small GTPase SAR1A: a key event underlying alcohol-induced Golgi fragmentation in hepatocytes.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Alcohol induces α2-6sialo mucin O-glycans that kill U937 macrophages mediated by sialic acid-binding immunoglobulin-like lectin 7 (Siglec 7).FEBS open bio · 2025Article
- Alcohol-induced Golgiphagy is triggered by the downregulation of Golgi GTPase RAB3D.Autophagy · 2024Article
- Targeting the ATF6-Mediated ER Stress Response and Autophagy Blocks Integrin-Driven Prostate Cancer Progression.Molecular cancer research : MCR · 2023Article
- Foot-and-Mouth Disease Virus 3A Hijacks Sar1 and Sec12 for ER Remodeling in a COPII-Independent Manner.Viruses · 2022Article
- Alcohol and Prostate Cancer: Time to Draw Conclusions.Biomolecules · 2022Review
- Alcohol-Induced Liver Injury: Down-regulation and Redistribution of Rab3D Results in Atypical Protein Trafficking.Hepatology communications · 2022Article
- Comparison of liver scintigraphy and the liver-spleen contrast in Gd-EOB-DTPA-enhanced MRI on liver function tests.Scientific reports · 2021Article
- Acetaldehyde suppresses HBV-MHC class I complex presentation on hepatocytes via induction of ER stress and Golgi fragmentation.American journal of physiology. Gastrointestinal and liver physiology · 2020Article
- Role of alcohol in pathogenesis of hepatitis B virus infection.World journal of gastroenterology · 2020Review
- Article
- Unlocking Golgi: Why Does Morphology Matter?Biochemistry. Biokhimiia · 2019Review
- Pluronic block copolymers enhance the anti-myeloma activity of proteasome inhibitors.Journal of controlled release : official journal of the Controlled Release Society · 2019Article
- Cross-Species Co-analysis of Prefrontal Cortex Chronic Ethanol Transcriptome Responses in Mice and Monkeys.Frontiers in molecular neuroscience · 2019Article
- The Role of Alcohol-Induced Golgi Fragmentation for Androgen Receptor Signaling in Prostate Cancer.Molecular cancer research : MCR · 2019Article
- Giantin Is Required for Post-Alcohol Recovery of Golgi in Liver Cells.Biomolecules · 2018Article
- THE IMPACT OF ALCOHOL ON PRO-METASTATIC N-GLYCOSYLATION IN PROSTATE CANCER.Krimskii zhurnal eksperimental'noi i klinicheskoi meditsiny = Kryms'kyi zhurnal eksperymental'noi ta klinichnoi medytsyny = Crimean journal of experimental and clinical medicine · 2018Article
- Disrupted ER-to-Golgi Trafficking Underlies Anti-HIV Drugs and Alcohol-Induced Cellular Stress and Hepatic Injury.Hepatology communications · 2017Article
- Ethanol exposure inhibits hepatocyte lipophagy by inactivating the small guanosine triphosphatase Rab7.Hepatology communications · 2017Article
- Dissecting the Role of Disturbed ER-Golgi Trafficking in Antivirals and Alcohol Abuse-Induced Pathogenesis of Liver Disorders.Journal of drug abuse · 2017Article
- Study of Ethanol-Induced Golgi Disorganization Reveals the Potential Mechanism of Alcohol-Impaired N-Glycosylation.Alcoholism, clinical and experimental research · 2016Article
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Authors and funding
4 authors.
Funding
Abstract
The hepatic asialoglycoprotein receptor (ASGP-R) is posttranslationally modified in the Golgi en route to the plasma membrane, where it mediates clearance of desialylated serum glycoproteins. It is known that content of plasma membrane-associated ASGP-R is decreased after ethanol exposure, although the mechanisms remain elusive. Previously, we found that formation of compact Golgi requires dimerization of the largest Golgi matrix protein giantin. We hypothesize that ethanol-impaired giantin function may be related to altered trafficking of ASGP-R. Here we report that in HepG2 cells expressing alcohol dehydrogenase and hepatocytes of ethanol-fed rats, ethanol metabolism results in Golgi disorganization. This process is initiated by dysfunction of SAR1A GTPase followed by altered COPII vesicle formation and impaired Golgi delivery of the protein disulfide isomerase A3 (PDIA3), an enzyme that catalyzes giantin dimerization. Additionally, we show that SAR1A gene silencing in hepatocytes mimics the effect of ethanol: dedimerization of giantin, arresting PDIA3 in the endoplasmic reticulum (ER) and large-scale alterations in Golgi architecture. Ethanol-induced Golgi fission has no effect on ER-to-Golgi transportation of ASGP-R, however, it results in its deposition in cis-medial-, but not trans-Golgi. Thus, alcohol-induced deficiency in COPII vesicle formation predetermines Golgi fragmentation which, in turn, compromises the Golgi-to-plasma membrane transportation of ASGP-R.
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