ArticleChemistry & biology2014
ERdj3 is an endoplasmic reticulum degradation factor for mutant glucocerebrosidase variants linked to Gaucher's disease.
Article in Chemistry & biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 76 citations in OpenAlex.
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- A PIKfyve modulator combined with an integrated stress response inhibitor to treat lysosomal storage diseases.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Activation and Purification of ß-Glucocerebrosidase by Exploiting its Transporter LIMP-2 - Implications for Novel Treatment Strategies in Gaucher's and Parkinson's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Turnover of EDEM1, an ERAD-enhancing factor, is mediated by multiple degradation routes.Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
- Lysosomal membrane integrity in fibroblasts derived from patients with Gaucher disease.Cell structure and function · 2024Article
- Glucocerebrosidase is imported into mitochondria and preserves complex I integrity and energy metabolism.Nature communications · 2023Article
- The GBA variant E326K is associated with alpha-synuclein aggregation and lipid droplet accumulation in human cell lines.Human molecular genetics · 2023Article
- Heat shock protein Hspa13 regulates endoplasmic reticulum and cytosolic proteostasis through modulation of protein translocation.The Journal of biological chemistry · 2022Article
- A plant reovirus hijacks the DNAJB12-Hsc70 chaperone complex to promote viral spread in its planthopper vector.Molecular plant pathology · 2022Article
- Regulation of Translation, Translocation, and Degradation of Proteins at the Membrane of the Endoplasmic Reticulum.International journal of molecular sciences · 2022Review
- Stress-responsive regulation of extracellular proteostasis.The Journal of cell biology · 2022Review
- Article
- Neuronopathic Gaucher disease: Beyond lysosomal dysfunction.Frontiers in molecular neuroscience · 2022Review
- Regulation of p53 and Cancer Signaling by Heat Shock Protein 40/J-Domain Protein Family Members.International journal of molecular sciences · 2021Review
- Loss of Function of Mutant IDS Due to Endoplasmic Reticulum-Associated Degradation: New Therapeutic Opportunities for Mucopolysaccharidosis Type II.International journal of molecular sciences · 2021Review
- A plant reovirus hijacks endoplasmic reticulum-associated degradation machinery to promote efficient viral transmission by its planthopper vector under high temperature conditions.PLoS pathogens · 2021Article
- Article
- Lysosome and Inflammatory Defects in GBA1-Mutant Astrocytes Are Normalized by LRRK2 Inhibition.Movement disorders : official journal of the Movement Disorder Society · 2020Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Gaucher's disease (GD) is caused by mutations that compromise β-glucocerebrosidase (GCase) folding in the endoplasmic reticulum (ER), leading to excessive degradation instead of trafficking, which results in insufficient lysosomal function. We hypothesized that ER GCase interacting proteins play critical roles in making quality control decisions, i.e., facilitating ER-associated degradation (ERAD) instead of folding and trafficking. Utilizing GCase immunoprecipitation followed by mass-spectrometry-based proteomics, we identified endogenous HeLa cell GCase protein interactors, including ERdj3, an ER resident Hsp40 not previously established to interact with GCase. Depleting ERdj3 reduced the rate of mutant GCase degradation in patient-derived fibroblasts, while increasing folding, trafficking, and function by directing GCase to the profolding ER calnexin pathway. Inhibiting ERdj3-mediated mutant GCase degradation while simultaneously enhancing calnexin-associated folding, by way of a diltiazem-mediated increase in ER Ca(2+) levels, yields a synergistic rescue of L444P GCase lysosomal function. Our findings suggest a combination therapeutic strategy for ameliorating GD.
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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.