ArticleNature2018
Role of glutamine synthetase in angiogenesis beyond glutamine synthesis.
Article in Nature, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
124 citing papers in PubMed, 1 synthesis or guideline pooled it, 216 citations in OpenAlex.
- Tools for investigating O-GlcNAc in signaling and other fundamental biological pathways.The Journal of biological chemistry · 2024Pooled it
- Glutamine Metabolism in Cardiac Hypertrophy.Reviews in cardiovascular medicine · 2026Review
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- Application of glutamine metabolism-related gene signatures in the non-invasive diagnosis of coronary artery disease: integrating bulk and single-cell transcriptomics.Journal of bioenergetics and biomembranes · 2026Article
- Plasma Exosomes Associated with Growth Divergence in High-Density Cultured Grass Carp (International journal of molecular sciences · 2026Article
- Metabolic characterization of the tumor microenvironment orchestrates therapeutic strategies and clinical outcomes in pancreatic cancer.Nature communications · 2026Article
- BMAL1 modulates glutamine supply to control haematopoietic stem and progenitor cell expansion.Development (Cambridge, England) · 2026Article
- Endothelial miR-7052 Safeguards Blood-Brain Barrier Integrity During Endotoxemia by Co-repressing ANGPT2 and PDE5A.Molecular neurobiology · 2026Article
- GLUL Confers Perivascular Cancer-Associated Fibroblasts With Pro-Angiogenic Capacity to Promote Glioma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Trustworthy prediction of enzyme commission numbers using a hierarchical interpretable transformer.Nature communications · 2026Article
- ZDHHC4-mediated ZEB-2 S-palmitoylation promotes melanoma epithelial-mesenchymal transition via deubiquitinating and stabilizing ZEB-2.Cellular and molecular life sciences : CMLS · 2026Article
- A Novel Gain-of-Function GLUL Variant Is Associated With Developmental and Epileptic Encephalopathy With Enlarged Perivascular Spaces.Human mutation · 2026Article
- Endothelial mitochondrial homeostasis in the development and progression of atherosclerosis.Frontiers in cardiovascular medicine · 2026Review
- Alpha-ketoglutarate promotes random-pattern skin flap survival by enhancing angiogenesis via PI3K/Akt/HIF-1α signaling pathway.Cell regeneration (London, England) · 2025Article
- Nitric oxide-releasing nanocarriers integrated with ginsenoside compound K in dissolvable microneedles for androgenetic alopecia.Journal of nanobiotechnology · 2025Article
- GLUL mediates FOXO3 O-GlcNAcylation to regulate the osteogenic differentiation of BMSCs and senile osteoporosis.Cell death and differentiation · 2025Article
- Endothelial cell metabolism in cardiovascular physiology and disease.Nature reviews. Cardiology · 2025Review
- Metabolomics Signatures of Atherosclerosis in Cardiovascular Disease: A Narrative Systematic Review.Journal of clinical medicine · 2025Review
- Site-1 protease-mediated cholesterol metabolism is essential for lymphatic development in mice.JCI insight · 2025Article
- Protein palmitoylation: A potential therapeutic target in cardiovascular diseases.Acta pharmaceutica Sinica. B · 2025Review
64 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
39 authors at 12 institutions in 7 countries.
Funding
Abstract
Glutamine synthetase, encoded by the gene GLUL, is an enzyme that converts glutamate and ammonia to glutamine. It is expressed by endothelial cells, but surprisingly shows negligible glutamine-synthesizing activity in these cells at physiological glutamine levels. Here we show in mice that genetic deletion of Glul in endothelial cells impairs vessel sprouting during vascular development, whereas pharmacological blockade of glutamine synthetase suppresses angiogenesis in ocular and inflammatory skin disease while only minimally affecting healthy adult quiescent endothelial cells. This relies on the inhibition of endothelial cell migration but not proliferation. Mechanistically we show that in human umbilical vein endothelial cells GLUL knockdown reduces membrane localization and activation of the GTPase RHOJ while activating other Rho GTPases and Rho kinase, thereby inducing actin stress fibres and impeding endothelial cell motility. Inhibition of Rho kinase rescues the defect in endothelial cell migration that is induced by GLUL knockdown. Notably, glutamine synthetase palmitoylates itself and interacts with RHOJ to sustain RHOJ palmitoylation, membrane localization and activation. These findings reveal that, in addition to the known formation of glutamine, the enzyme glutamine synthetase shows unknown activity in endothelial cell migration during pathological angiogenesis through RHOJ palmitoylation.
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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.