Transferrin receptor 2 is a component of the erythropoietin receptor complex and is required for efficient erythropoiesis
Abstract
Erythropoietin (Epo) is required for erythroid progenitor differentiation. Although Epo crosslinking experiments have revealed the presence of Epo receptor (EpoR)–associated proteins that could never be identified, EpoR is considered to be a paradigm for homodimeric cytokine receptors. We purified EpoR-binding partners and identified the type 2 transferrin receptor (TfR2) as a component of the EpoR complex corresponding to proteins previously detected in cross-linking experiments. TfR2 is involved in iron metabolism by regulating hepcidin production in liver cells. We show that TfR2 and EpoR are synchronously coexpressed during the differentiation of erythroid progenitors. TfR2 associates with EpoR in the endoplasmic reticulum and is required for the efficient transport of this receptor to the cell surface. Erythroid progenitors from TfR2−/−mice show a decreased sensitivity to Epo and increased circulating Epo levels. In human erythroid progenitors, TfR2 knockdown delays the terminal differentiation. Erythroid cells produce growth differentiation factor-15, a cytokine that suppresses hepatic hepcidin production in certain erythroid diseases such as thalassemia. We show that the production of growth differentiation factor-15 by erythroid cells is dependent on both Epo and TfR2. Taken together, our results show that TfR2 exhibits a non hepatic function as a component of the EpoR complex and is required for efficient erythropoiesis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The erythroid response to iron restriction is optimized by the iron sensor TFR2, a partner of the erythropoietin receptor.
“Finally the erythroid response to iron restriction is optimized by the iron sensor TFR2, a partner of erythropoietin receptor.10”
From Iron metabolism and iron disorders revisited in the hepcidin era (2020) · cites this paper as [10]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Transferrin receptor is necessary for development of erythrocytes and the nervous system
Levy, J. E., Jin, O., Fujiwara, Y., Kuo, F., & Andrews, N. (1999) · Nature Genetics · doi:10.1038/7727 · Cited by 574 · see citing works
Gao, J., Chen, J., Kramer, M., Tsukamoto, H., Zhang, A.-S., & Enns, C. A. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.01.010 · Cited by 326 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
A Red carpet for iron metabolism
Muckenthaler, M. U., Rivella, S., Hentze, M. W., & Galy, B. (2017) · Cell · doi:10.1016/j.cell.2016.12.034 · Cited by 1,319 · see citing works
Iron metabolism and iron disorders revisited in the hepcidin era
Camaschella, C., Nai, A., & Silvestri, L. (2020) · Haematologica · doi:10.3324/haematol.2019.232124 · Cited by 734 · see citing works
“Finally the erythroid response to iron restriction is optimized by the iron sensor TFR2, a partner of erythropoietin receptor.(10) Loss of bone marrow TFR2 in mice increases the sensitivity of erythroblasts to erythropoietin, which causes erythrocytosis, especially in iron deficiency.”
Self-citationGinzburg, Y., & Rivella, S. (2011) · Blood · doi:10.1182/blood-2011-03-283614 · Cited by 201 · see citing works
Novel loci affecting iron homeostasis and their effects in individuals at risk for hemochromatosis
Benyamin, B., Esko, T., Ried, J. S., Radhakrishnan, A., Vermeulen, S. H., Traglia, M., Gögele, M., Anderson, D., Broer, L., Podmore, C., et al. (2014) · Nature Communications · doi:10.1038/ncomms5926 · Cited by 30 · see citing works
“TfR2 variation could also affect these iron parameters through its effect on erythropoiesis 35 .”
Self-citation
- Authors
- Forejtnikovà, H., Vieillevoye, M., Zermati, Y., Lambert, M., Pellegrino, R. M., Guihard, S., Gaudry, M., Camaschella, C., Lacombe, C., Roetto, A., Mayeux, P., & Verdier, F.
- Affiliations
- Institut Cochin, Université Paris Descartes, Centre National de la recherche Scientifique (Unité Mixte de Recherche 8104), Paris, France;
- Centre National de la Recherche Scientifique (FR)
- University of Turin (IT)
- Vita-Salute San Raffaele University (IT)
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2010-12-09
- Volume
- 116
- Issue
- 24
- Pages
- 5357-5367
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2033380296
- Cited by
- 152
- References
- 2
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 7 · 2023: 12 · 2022: 9 · 2021: 10 · 2020: 12 · 2019: 12 · 2018: 12 · 2017: 12 · 2016: 8 · 2015: 11 · 2014: 10 · 2013: 4 · 2012: 9
- FWCI
- 4.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Funders
- Erasmus Medisch Centrum
- Ligue Contre le Cancer
- Erasmus Universitair Medisch Centrum Rotterdam
- Erasmus+
- Topics
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- transferrin receptor 2, erythropoietin receptor, erythropoiesis, erythroid progenitor differentiation, receptor complex, endoplasmic reticulum, growth differentiation factor 15, hepcidin, iron metabolism, erythropoietin sensitivity, thalassemia
- MeSH terms
- Animals, Cell Differentiation, Erythropoiesis, Gene Expression Regulation, Receptors, Transferrin, Receptors, Erythropoietin, Mice, Knockout, Protein Transport, Multiprotein Complexes, Mice, Growth Differentiation Factor 15
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
