ArticleCommunications biology2018
Mannosidase activity of EDEM1 and EDEM2 depends on an unfolded state of their glycoprotein substrates.
Article in Communications biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 58 citations in OpenAlex.
- Studying Glycan-Dependent ERAD of Misfolded Glycoproteins in Plants.Methods in molecular biology (Clifton, N.J.) · 2026Article
- N-glycan-dependent protein maturation and quality control in the ER.Nature reviews. Molecular cell biology · 2025Review
- Unique N-glycosylation signatures in human iPSC derived microglia activated by Aβ oligomer and lipopolysaccharide.Scientific reports · 2025Article
- Protein degrons and degradation: Exploring substrate recognition and pathway selection in plants.The Plant cell · 2024Review
- Characterising the genetic architecture of changes in adiposity during adulthood using electronic health records.Nature communications · 2024Article
- StaufenC facilitates utilization of the ERAD pathway to transport dsRNA through the endoplasmic reticulum to the cytosol.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Turnover of EDEM1, an ERAD-enhancing factor, is mediated by multiple degradation routes.Genes to cells : devoted to molecular & cellular mechanisms · 2024Article
- Thioredoxin Domain Containing 5 (TXNDC5): Friend or Foe?Current issues in molecular biology · 2024Review
- HCMV US2 co-opts TRC8 to degrade the endoplasmic reticulum-resident protein LMAN2L.The Journal of general virology · 2024Article
- Mechanisms of substrate processing during ER-associated protein degradation.Nature reviews. Molecular cell biology · 2023Review
- Identification of EGF Receptor and Thrombospondin-1 as Endogenous Targets of ER-Associated Degradation Enhancer EDEM1 in HeLa Cells.International journal of molecular sciences · 2023Article
- Systematic analysis of the prognosis and immune infiltration of E2Fs in thyroid carcinoma.Frontiers in genetics · 2023Article
- Expression analysis and functional characterization of thioredoxin domain-containing protein 11.Molecular biology reports · 2022Article
- Oligomannose-Type Glycan Processing in the Endoplasmic Reticulum and Its Importance in Misfolding Diseases.Biology · 2022Review
- A Predominant Role of AtEDEM1 in Catalyzing a Rate-Limiting Demannosylation Step of an Arabidopsis Endoplasmic Reticulum-Associated Degradation Process.Frontiers in plant science · 2022Article
- EDEM1 Regulates Amyloid Precursor Protein (APP) Metabolism and Amyloid-β Production.International journal of molecular sciences · 2021Article
- Article
- Role and mechanism of chaperones calreticulin and ERP57 in restoring trafficking to mutant HERG‑A561V protein.International journal of molecular medicine · 2021Article
- Bi-allelic variants in the ER quality-control mannosidase gene EDEM3 cause a congenital disorder of glycosylation.American journal of human genetics · 2021Article
- Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Extensive mannose trimming of nascent glycoprotein N-glycans signals their targeting to endoplasmic reticulum-associated degradation (ERAD). ER mannosidase I (ERManI) and the EDEM protein family participate in this process. However, whether the EDEMs are truly mannosidases can be addressed only by measuring mannosidase activity in vitro. Here, we reveal EDEM1 and EDEM2 mannosidase activities in vitro. Whereas ERManI significantly trims free N-glycans, activity of the EDEMs is modest on free oligosaccharides and on glycoproteins. However, mannosidase activity of ERManI and the EDEMs is significantly higher on a denatured glycoprotein. The EDEMs associate with oxidoreductases, protein disulfide isomerase, and especially TXNDC11, enhancing mannosidase activity on glycoproteins but not on free N-glycans. The finding that substrate unfolded status increases mannosidase activity solves an important conundrum, as current models suggest general slow mannose trimming. As we show, misfolded or unfolded glycoproteins are subject to differentially faster trimming (and targeting to ERAD) than well-folded ones.
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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.