ArticleMolecular biology of the cell2011
Mannose-6-phosphate regulates destruction of lipid-linked oligosaccharides.
Article in Molecular biology of the cell, 2011. 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, 34 citations in OpenAlex.
- Structural basis of G6P/Pi transport and inhibition in SLC37A4.Nature structural & molecular biology · 2026Article
- Integrated Multi-Omics Analysis Reveals Key Regulators of Bovine Oocyte Maturation.International journal of molecular sciences · 2025Article
- A genome-wide CRISPR screen identifies DPM1 as a modifier of DPAGT1 deficiency and ER stress.PLoS genetics · 2022Article
- Article
- New Insights into Immunological Involvement in Congenital Disorders of Glycosylation (CDG) from a People-Centric Approach.Journal of clinical medicine · 2020Article
- Targeting STT3A-oligosaccharyltransferase with NGI-1 causes herpes simplex virus 1 dysfunction.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- A bioactive mammalian disaccharide associated with autoimmunity activates STING-TBK1-dependent immune response.Nature communications · 2019Article
- Mammalian STT3A/B oligosaccharyltransferases segregate N-glycosylation at the translocon from lipid-linked oligosaccharide hydrolysis.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Synaptic roles for phosphomannomutase type 2 in a new Drosophila congenital disorder of glycosylation disease model.Disease models & mechanisms · 2016Article
- trappc11 is required for protein glycosylation in zebrafish and humans.Molecular biology of the cell · 2016Article
- Cytosolic Nuclease TREX1 Regulates Oligosaccharyltransferase Activity Independent of Nuclease Activity to Suppress Immune Activation.Immunity · 2015Article
- Generation and degradation of free asparagine-linked glycans.Cellular and molecular life sciences : CMLS · 2015Review
- Role of the unfolded protein response in regulating the mucin-dependent filamentous-growth mitogen-activated protein kinase pathway.Molecular and cellular biology · 2015Article
- Genetic defects in dolichol metabolism.Journal of inherited metabolic disease · 2015Review
- Mannose metabolism: more than meets the eye.Biochemical and biophysical research communications · 2014Review
- Letter to the Glycoforum: Improved protocols for preparing lipid-linked and related saccharides for Fluorophore-Assisted Carbohydrate Electrophoresis (FACE).Glycobiology · 2013Article
- Glycoprotein biosynthesis in a eukaryote lacking the membrane protein Rft1.The Journal of biological chemistry · 2013Article
- Understanding human glycosylation disorders: biochemistry leads the charge.The Journal of biological chemistry · 2013Review
- A zebrafish model of congenital disorders of glycosylation with phosphomannose isomerase deficiency reveals an early opportunity for corrective mannose supplementation.Disease models & mechanisms · 2013Article
- Regulation of protein glycosylation and sorting by the Golgi matrix proteins GRASP55/65.Nature communications · 2013Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Mannose-6-phosphate (M6P) is an essential precursor for mannosyl glycoconjugates, including lipid-linked oligosaccharides (LLO; glucose(3)mannose(9)GlcNAc(2)-P-P-dolichol) used for protein N-glycosylation. In permeabilized mammalian cells, M6P also causes specific LLO cleavage. However, the context and purpose of this paradoxical reaction are unknown. In this study, we used intact mouse embryonic fibroblasts to show that endoplasmic reticulum (ER) stress elevates M6P concentrations, leading to cleavage of the LLO pyrophosphate linkage with recovery of its lipid and lumenal glycan components. We demonstrate that this M6P originates from glycogen, with glycogenolysis activated by the kinase domain of the stress sensor IRE1-α. The apparent futility of M6P causing destruction of its LLO product was resolved by experiments with another stress sensor, PKR-like ER kinase (PERK), which attenuates translation. PERK's reduction of N-glycoprotein synthesis (which consumes LLOs) stabilized steady-state LLO levels despite continuous LLO destruction. However, infection with herpes simplex virus 1, an N-glycoprotein-bearing pathogen that impairs PERK signaling, not only caused LLO destruction but depleted LLO levels as well. In conclusion, the common metabolite M6P is also part of a novel mammalian stress-signaling pathway, responding to viral stress by depleting host LLOs required for N-glycosylation of virus-associated polypeptides. Apparently conserved throughout evolution, LLO destruction may be a response to a variety of environmental stresses.
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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.