ArticleNature communications2021
Regulation of local GTP availability controls RAC1 activity and cell invasion.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
What it found
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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.
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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.
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Who cites it
33 citing papers in PubMed, 41 citations in OpenAlex.
- GTP biosynthesis is a therapeutic vulnerability in Rac1-mutant melanoma.bioRxiv : the preprint server for biology · 2026Article
- RhoG, Rac1 and Cdc42 cooperation in cell protrusion revealed by multiplexed optogenetics and biosensor imaging.bioRxiv : the preprint server for biology · 2026Article
- Pharmacological Mechanisms of Ursolic Acid Derivative Against Prostate Cancer via Regulating Cytoskeletal Homeostasis and Apoptotic Pathways.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Treatment of age-related decreases in GTP levels restores endocytosis and autophagy.GeroScience · 2026Article
- Coiled-coil homo-oligomerization and disaggregase Hsp104 act in parallel to stabilize orphan septins.bioRxiv : the preprint server for biology · 2026Article
- Decoding Rho GTPase signalling networks in directed cell migration.Frontiers in cell and developmental biology · 2026Review
- Inhibitors of De Novo Guanylate Biosynthesis Enhance the Potency of MAPK Cascade Inhibitors Against Colorectal Cancer.International journal of molecular sciences · 2025Article
- An IMPDH2 variant associated with neurodevelopmental disorder disrupts purine biosynthesis and somite organization.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Inhibition of the RAC/PAK Signaling Axis Enhances the Potency of MAPK Cascade Inhibitors Against Uveal Melanoma.Biomolecules · 2025Article
- Y12C mutation disrupts IMPDH cytoophidia and alters cancer metabolism.The FEBS journal · 2025Article
- Effects of NaCell biochemistry and biophysics · 2025Review
- Leveraging AAV1-Rac1T17N to prevent experimental proliferative vitreoretinopathy.Journal of translational medicine · 2025Article
- Inosine monophosphate dehydrogenase 2 (IMPDH2) modulates response to therapy and chemo-resistance in triple negative breast cancer.Scientific reports · 2025Article
- Lower ratio of IMPDH1 to IMPDH2 sensitizes gliomas to chemotherapy.Cancer gene therapy · 2024Article
- Nucleocytoplasmic transport rates are regulated by cellular processes that modulate GTP availability.The Journal of cell biology · 2024Article
- Integrative single-cell and bulk transcriptomes analyses reveals heterogeneity of serine-glycine-one-carbon metabolism with distinct prognoses and therapeutic vulnerabilities in HNSCC.International journal of oral science · 2024Article
- Decreased Tiam1-mediated Rac1 activation is responsible for impaired directional persistence of chondrocyte migration in microtia.Journal of cellular and molecular medicine · 2024Article
- To label or not: the need for validation in label-free imaging.Journal of biomedical optics · 2024Review
- GTP Signaling Links Metabolism, DNA Repair, and Responses to Genotoxic Stress.Cancer discovery · 2024Article
- Epigenetic silencing ofEpigenomics · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
24 authors at 7 institutions in 1 country.
Funding
Abstract
Physiological changes in GTP levels in live cells have never been considered a regulatory step of RAC1 activation because intracellular GTP concentration (determined by chromatography or mass spectrometry) was shown to be substantially higher than the in vitro RAC1 GTP dissociation constant (RAC1-GTP Kd). Here, by combining genetically encoded GTP biosensors and a RAC1 activity biosensor, we demonstrated that GTP levels fluctuating around RAC1-GTP Kd correlated with changes in RAC1 activity in live cells. Furthermore, RAC1 co-localized in protrusions of invading cells with several guanylate metabolism enzymes, including rate-limiting inosine monophosphate dehydrogenase 2 (IMPDH2), which was partially due to direct RAC1-IMPDH2 interaction. Substitution of endogenous IMPDH2 with IMPDH2 mutants incapable of binding RAC1 did not affect total intracellular GTP levels but suppressed RAC1 activity. Targeting IMPDH2 away from the plasma membrane did not alter total intracellular GTP pools but decreased GTP levels in cell protrusions, RAC1 activity, and cell invasion. These data provide a mechanism of regulation of RAC1 activity by local GTP pools in live cells.
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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.