scholarly journals Temporal manipulation of transferrin-receptor-1-dependent iron uptake identifies a sensitive period in mouse hippocampal neurodevelopment

Hippocampus ◽  
2012 ◽  
Vol 22 (8) ◽  
pp. 1691-1702 ◽  
Author(s):  
S.J.B. Fretham ◽  
E.S. Carlson ◽  
J. Wobken ◽  
P.V. Tran ◽  
A. Petryk ◽  
...  
Keyword(s):  
Transferrin Receptor ◽  
Iron Uptake ◽  
Sensitive Period ◽  
Transferrin Receptor 1

scholarly journals Transferrin receptor 1-mediated iron uptake plays an essential role in hematopoiesis

Haematologica ◽  
2019 ◽  
Vol 105 (8) ◽  
pp. 2071-2082 ◽  
Author(s):  
Shufen Wang ◽  
Xuyan He ◽  
Qian Wu ◽  
Li Jiang ◽  
Liyun Chen ◽  
...  
Keyword(s):  
Transferrin Receptor ◽  
Iron Uptake ◽  
Essential Role ◽  
Transferrin Receptor 1

scholarly journals Understanding the Transferrin Receptor and Cellular Iron Deficiency Outside the Erythron

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. SCI-42-SCI-42
Author(s):  
Nancy C. Andrews
Keyword(s):  
Iron Deficiency ◽  
Missense Mutation ◽  
Transferrin Receptor ◽  
Iron Uptake ◽  
Clinical Manifestations ◽  
Cell Types ◽  
Conditional Knockout ◽  
Deficiency Anemia ◽  
Transferrin Receptor 1

Our laboratory showed that mouse embryos lacking the classical transferrin receptor, Tfrc, experienced anemia, pericardial effusion and a kinking of the neural tube, but otherwise appeared to be developing normally, suggesting that Tfrc was not needed by most tissues (Levy et al. 1999). Subsequently, we reported that Tfrc was essential for hematopoiesis but seemed to be dispensable in other tissues (Ned et al., 2003). A recent paper showing that a missense mutation in the TFRC internalization motif resulted in immunodeficiency without other clinical manifestations was consistent with this idea (Jabara et al., 2016). Nonetheless, we were not entirely convinced. More than thirty years ago, Larrick and Hyman described a patient with an anti-TFRC autoantibody who suffered from a broader range of clinical problems, suggesting that TFRC might have other roles (Larrick and Hyman, 1984). To help resolve the issue, we developed mice carrying an allele of Tfrc that can be conditionally inactivated, and used Cre/lox-mediated recombination to disrupt that allele in vivo, in several key cell types. We asked two questions: (1) is Tfrc important in those cell types and, if so, (2) what are the cellular consequences of Tfrc loss? We found that some cell types do not need Tfrc but others are highly dependent upon it. Those cell types that depend upon Tfrc generally need it for iron uptake, as expected, with one exception. Tfrc is critically important for normal development of the intestinal epithelium, but our data indicate that its essential role does not involve iron uptake. While surprising in view of our earlier results, the roles of Tfrc that we have unmasked through conditional knockout experiments would not have been apparent prior to the death of global Tfrc knockout embryos in mid-gestation. Nonetheless those roles are important, and our results give insight into why iron deficiency exacerbates heart failure, how muscle iron deficiency leads to disruption of systemic carbon metabolism, and how iron deficiency, rather than iron excess, may play a role in the pathogenesis of neurodegenerative disorders. Levy JE, Jin O, Fujiwara Y, Kuo F, Andrews NC. Transferrin receptor is necessary for development of erythrocytes and the nervous system. Nat Genet. 1999;21:396-9. Ned RM, Swat W, Andrews NC. Transferrin receptor 1 is differentially required in lymphocyte development. Blood. 2003;102:3711-8. Jabara HH, Boyden SE, Chou J et al. A missense mutation in TFRC, encoding transferrin receptor 1, causes combined immunodeficiency. Nat Genet. 2016;48:74-8. Larrick JW, Hyman ES. Acquired iron-deficiency anemia caused by an antibody against the transferrin receptor. N Engl J Med. 1984;311:214-8. Disclosures Andrews: Novartis: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Src Regulates Tyr20 Phosphorylation of Transferrin Receptor-1 and Potentiates Breast Cancer Cell Survival

2011 ◽  
Vol 286 (41) ◽  
pp. 35708-35715 ◽  
Author(s):  
Jinlong Jian ◽  
Qing Yang ◽  
Xi Huang
Keyword(s):  
Breast Cancer ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Transferrin Receptor ◽  
Iron Uptake ◽  
Caspase 3 ◽  
Transferrin Receptor 1 ◽  
Cancer Cell Survival

Transferrin receptor 1 (TfR1) is a ubiquitous type II membrane receptor with 61 amino acids in the N-terminal cytoplasmic region. TfR1 is highly expressed in cancer cells, particularly under iron deficient conditions. Overexpression of TfR1 is thought to meet the increased requirement of iron uptake necessary for cell growth. In the present study, we used transferrin (Tf), a known ligand of TfR1, and gambogic acid (GA), an apoptosis-inducing agent and newly identified TfR1 ligand to investigate the signaling role of TfR1 in breast cancer cells. We found that GA but not Tf induced apoptosis in a TfR1-dependent manner in breast cancer MDA-MB-231 cells. Estrogen receptor-positive MCF-7 cells lack caspase-3 and were not responsive to GA treatment. GA activated the three major signaling pathways of the MAPK family, as well as caspase-3, -8, and Poly(ADP-ribose)polymerase apoptotic pathway. Interestingly, only Src inhibitor PP2 greatly sensitized the cells to GA-mediated apoptosis. Further investigations by confocal fluorescence microscopy and immunoprecipitation revealed that Src and TfR1 are constitutively bound. Using TfR1-deficient CHO TRVB cells, point mutation studies showed that Tyr20 within the 20YTRF23 motif of the cytoplasmic region of TfR1 is the phosphorylation site by Src. TfR1 Tyr20 phosphomutants were more sensitive to GA-mediated apoptosis. Our results indicate that, albeit its iron uptake function, TfR1 is a signaling molecule and tyrosine phosphorylation at position 20 by Src enhances anti-apoptosis and potentiates breast cancer cell survival.

scholarly journals Noncanonical role of transferrin receptor 1 is essential for intestinal homeostasis

2015 ◽  
Vol 112 (37) ◽  
pp. 11714-11719 ◽  
Author(s):  
Alan C. Chen ◽  
Adriana Donovan ◽  
Renee Ned-Sykes ◽  
Nancy C. Andrews
Keyword(s):  
Intestinal Epithelium ◽  
Transferrin Receptor ◽  
Iron Uptake ◽  
Epithelial To Mesenchymal Transition ◽  
Early Death ◽  
Stem Cell Markers ◽  
Intestinal Epithelial ◽  
Mesenchymal Transition ◽  
Cellular Iron ◽  
Transferrin Receptor 1

Transferrin receptor 1 (Tfr1) facilitates cellular iron uptake through receptor-mediated endocytosis of iron-loaded transferrin. It is expressed in the intestinal epithelium but not involved in dietary iron absorption. To investigate its role, we inactivated the Tfr1 gene selectively in murine intestinal epithelial cells. The mutant mice had severe disruption of the epithelial barrier and early death. There was impaired proliferation of intestinal epithelial cell progenitors, aberrant lipid handling, increased mRNA expression of stem cell markers, and striking induction of many genes associated with epithelial-to-mesenchymal transition. Administration of parenteral iron did not improve the phenotype. Surprisingly, however, enforced expression of a mutant allele of Tfr1 that is unable to serve as a receptor for iron-loaded transferrin appeared to fully rescue most animals. Our results implicate Tfr1 in homeostatic maintenance of the intestinal epithelium, acting through a role that is independent of its iron-uptake function.

scholarly journals Transferrin receptor 1-mediated iron uptake regulates bone mass in mice via osteoclast mitochondria and cytoskeleton

2021 ◽  
Author(s):  
Haibo Zhao ◽  
Bhaba K Das ◽  
Lei Wang ◽  
Toshifumi Fujiwara ◽  
Jian Zhou ◽  
...  
Keyword(s):  
Bone Mass ◽  
Trabecular Bone ◽  
Transferrin Receptor ◽  
Iron Uptake ◽  
Energy Demand ◽  
Osteoclast Differentiation ◽  
High Energy ◽  
Long Bones ◽  
Intracellular Iron ◽  
Transferrin Receptor 1

Increased intracellular iron spurs mitochondrial biogenesis and respiration to satisfy high-energy demand during osteoclast differentiation and bone-resorbing activities. Transferrin receptor 1 (TFR1) mediates cellular iron uptake through endocytosis of iron-loaded transferrin and its expression increases during osteoclast differentiation. Nonetheless, the precise functions of TFR1 and TFR1-mediated iron uptake in osteoclast biology and skeletal homeostasis remain incompletely understood. To investigate the role of TFR1 in osteoclast lineage cells, we conditionally deleted Tfr1 gene in myeloid precursors or mature osteoclasts by crossing Tfr1-floxed mice with LysM-Cre and Ctsk-Cre mice, respectively. Skeletal phenotyping by μCT and histology unveiled that loss of Tfr1 in osteoclast progenitor cells resulted in a three-fold increase in trabecular bone mass in the long bones of 10-week old female but not male mice. Although high trabecular bone volume in long bones was seen in both male and female mice with deletion of Tfr1 in mature osteoclasts, this phenotype was more pronounced in female knockout mice. Mechanistically, disruption of Tfr1 expression attenuated mitochondrial metabolism and cytoskeletal organization in mature osteoclasts, leading to decreased bone resorption with no impact on osteoclastogenesis. These results indicate that Tfr1-mediated iron uptake is specifically required for osteoclast function and is indispensable for bone remodeling.

Heat shock protein 27 downregulates the transferrin receptor 1-mediated iron uptake

2006 ◽  
Vol 38 (8) ◽  
pp. 1402-1416 ◽  
Author(s):  
Huaiyong Chen ◽  
Chunlei Zheng ◽  
Yong Zhang ◽  
Yan-Zhong Chang ◽  
Zhong-Ming Qian ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Transferrin Receptor ◽  
Iron Uptake ◽  
Heat Shock Protein 27 ◽  
Transferrin Receptor 1
Sign in / Sign up

Export Citation Format

Share Document