ArticleCurrent biology : CB2015
Peters plus syndrome mutations disrupt a noncanonical ER quality-control mechanism.
Article in Current biology : CB, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 2 of them syntheses that pooled it.
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Who cites it
59 citing papers in PubMed, 2 syntheses or guidelines pooled it, 82 citations in OpenAlex.
- Metabolic Cardiomyopathies and Cardiac Defects in Inherited Disorders of Carbohydrate Metabolism: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Cardiac complications of congenital disorders of glycosylation (CDG): a systematic review of the literature.Journal of inherited metabolic disease · 2017Pooled it
- Crystal structure of a β1,3-Glucosyltransferase reveals an unusual substrate recognition by a two-domain GT-A fold glycosyltransferase.The Journal of biological chemistry · 2026Article
- Phosphomimetic Thrombospondin-1 Modulates Integrin β1-FAK Signaling and Vascular Cell Functions.Biomolecules · 2026Article
- Diagnostic Utility of Next-Generation Sequencing-based CNV Analysis in Eleven Patients with Peters-Plus Syndrome: A Single-Center ExperienceJournal of clinical research in pediatric endocrinology · 2025Article
- Identifying Genes Associated with the Anticancer Activity of a Fluorinated Chalcone in Triple-Negative Breast Cancer Cells Using Bioinformatics Tools.International journal of molecular sciences · 2025Article
- FUT10 and FUT11 are protein O-fucosyltransferases that modify protein EMI domains.Nature chemical biology · 2025Article
- ProteinMolecules (Basel, Switzerland) · 2025Review
- Genetics of suicide ideation. A role for inflammation and neuroplasticity?European archives of psychiatry and clinical neuroscience · 2024Article
- Congenital anterior segment ocular disorders: Genotype-phenotype correlations and emerging novel mechanisms.Progress in retinal and eye research · 2024Review
- Cardiomyopathy, an uncommon phenotype of congenital disorders of glycosylation: Recommendations for baseline screening and follow-up evaluation.Molecular genetics and metabolism · 2024Article
- POFUT1 promotes gastric cancer progression through Notch/Wnt dual signaling pathways dependent on the parafibromin-NICD1-β-catenin complex.Journal of the Chinese Medical Association : JCMA · 2023Article
- O-fucosylation of thrombospondin type I repeats is dispensable for trafficking thrombospondin 1 to platelet secretory granules.Glycobiology · 2023Article
- Passing the post: roles of posttranslational modifications in the form and function of extracellular matrix.American journal of physiology. Cell physiology · 2023Review
- Tryptophan C-mannosylation is critical for Plasmodium falciparum transmission.Nature communications · 2022Article
- Structure and Function of Potential Glycosylation Sites of Dynactin-Associated Protein dynAP.Molecular biotechnology · 2022Article
- O-fucosylation stabilizes the TSR3 motif in thrombospondin-1 by interacting with nearby amino acids and protecting a disulfide bond.The Journal of biological chemistry · 2022Article
- O-fucosylation of thrombospondin type 1 repeats is essential for ECM remodeling and signaling during bone development.Matrix biology : journal of the International Society for Matrix Biology · 2022Article
- Generation of Properly Folded Epidermal Growth Factor-Like (EGF) Repeats and Glycosyltransferases Enables In Vitro O-Glycosylation.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Hydrocephalus in mouse B3glct mutants is likely caused by defects in multiple B3GLCT substrates in ependymal cells and subcommissural organ.Glycobiology · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundO-fucose is added to cysteine-rich domains called thrombospondin type 1 repeats (TSRs) by protein O-fucosyltransferase 2 (POFUT2) and is elongated with glucose by β3-glucosyltransferase (B3GLCT). Mutations in B3GLCT result in Peters plus syndrome (PPS), an autosomal recessive disorder characterized by eye and other developmental defects. Although 49 putative targets are known, the function of the disaccharide and its role in PPS remain unexplored.
resultsHere we show that while POFUT2 is required for secretion of all targets tested, B3GLCT only affects the secretion of a subset, consistent with the observation that B3GLCT mutant phenotypes in PPS patients are less severe than embryonic lethal phenotypes of Pofut2-null mice. O-glycosylation occurs cotranslationally, as TSRs fold. Mass spectral analysis reveals that TSRs from mature, secreted protein are stoichiometrically modified with the disaccharide, whereas TSRs from protein still folding in the ER are partially modified, suggesting that O-glycosylation marks folded TSRs and promotes ER exit. In vitro unfolding assays demonstrate that fucose and glucose stabilize folded TSRs in an additive manner. In vitro refolding assays under redox conditions showed that POFUT2 recognizes, glycosylates, and stabilizes the folded form of TSRs, resulting in a net acceleration of folding.
conclusionsWhile known ER quality-control machinery rely on identifying and tagging unfolded proteins, we find that POFUT2 and B3GLCT mediate a noncanonical ER quality-control mechanism that recognizes folded TSRs and stabilizes them by glycosylation. Our findings provide a molecular basis for the defects observed in PPS and potential targets that contribute to the pathology.
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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.