ArticleBlood2011
Silencing of RhoA nucleotide exchange factor, ARHGEF3, reveals its unexpected role in iron uptake.
Article in Blood, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 4 of them syntheses that pooled it.
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.
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
20 citing papers in PubMed, 4 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- Pooled it
- Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits.American journal of human genetics · 2016Pooled it
- A loss of function screen of identified genome-wide association study Loci reveals new genes controlling hematopoiesis.PLoS genetics · 2014Pooled it
- Pooled it
- Interactions with polygenic background impact quantitative traits in the UK Biobank.medRxiv : the preprint server for health sciences · 2025Article
- Secondary analyses for genome-wide association studies using expression quantitative trait loci.Genetic epidemiology · 2022Article
- Rho/ROCK Pathway and Noncoding RNAs: Implications in Ischemic Stroke and Spinal Cord Injury.International journal of molecular sciences · 2021Review
- Role of ARHGEF3 as a GEF and mTORC2 Regulator.Frontiers in cell and developmental biology · 2021Review
- Genetic architecture of host proteins involved in SARS-CoV-2 infection.Nature communications · 2020Article
- Article
- ARHGEF12 regulates erythropoiesis and is involved in erythroid regeneration after chemotherapy in acute lymphoblastic leukemia patients.Haematologica · 2020Article
- Comprehensive population-based genome sequencing provides insight into hematopoietic regulatory mechanisms.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Article
- Total saponins of panaxnotoginseng promotes lymphangiogenesis by activation VEGF-C expression of lymphatic endothelial cells.Journal of ethnopharmacology · 2016Article
- The putative tumor activator ARHGEF3 promotes nasopharyngeal carcinoma cell pathogenesis by inhibiting cellular apoptosis.Oncotarget · 2016Article
- From GWAS to function: lessons from blood cells.ISBT science series · 2016Article
- ARHGEF3 controls HDACi-induced differentiation via RhoA-dependent pathways in acute myeloid leukemias.Epigenetics · 2015Article
- RhoGEFs in cell motility: novel links between Rgnef and focal adhesion kinase.Current molecular medicine · 2014Review
- Zebrafish in the sea of mineral (iron, zinc, and copper) metabolism.Frontiers in pharmacology · 2014Review
- Imputation of exome sequence variants into population- based samples and blood-cell-trait-associated loci in African Americans: NHLBI GO Exome Sequencing Project.American journal of human genetics · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Genomewide association meta-analysis studies have identified > 100 independent genetic loci associated with blood cell indices, including volume and count of platelets and erythrocytes. Although several of these loci encode known regulators of hematopoiesis, the mechanism by which most sequence variants exert their effect on blood cell formation remains elusive. An example is the Rho guanine nucleotide exchange factor, ARHGEF3, which was previously implicated by genomewide association meta-analysis studies in bone cell biology. Here, we report on the unexpected role of ARHGEF3 in regulation of iron uptake and erythroid cell maturation. Although early erythroid differentiation progressed normally, silencing of arhgef3 in Danio rerio resulted in microcytic and hypochromic anemia. This was rescued by intracellular supplementation of iron, showing that arhgef3-depleted erythroid cells are fully capable of hemoglobinization. Disruption of the arhgef3 target, RhoA, also produced severe anemia, which was, again, corrected by iron injection. Moreover, silencing of ARHGEF3 in erythromyeloblastoid cells K562 showed that the uptake of transferrin was severely impaired. Taken together, this is the first study to provide evidence for ARHGEF3 being a regulator of transferrin uptake in erythroid cells, through activation of RHOA.
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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.