Disease relevance of Tfrc

• At all stages of differentiation in our study, transferrin receptor expression in bone marrow erythroid cells in Fech(m1Pas) was normal in mutant mice but not in patients with iron-deficiency anemia [1].
• Tf-beta-galactosidase plasmid conjugate thus constructed was specifically transfected to human erythroleukemia cells (K562) via Tf-R without the aid of any lysosomotropic agents [2].
• Identification of the segments of the mouse transferrin receptor 1 required for mouse mammary tumor virus infection [3].
• Hepatic and/or duodenal response patterns of iron metabolism genes, such as Trfr, cybrd1, and Slc11a2, explained the transition from early postnatal iron deficiency to iron overload by 12 weeks of age [4].
• Both melanomas and normal nevi expressed human Ia-like antigens, transferrin receptor and the transferrin-related molecule p97 [5].

Psychiatry related information on Tfrc

• Taken together, these data demonstrate that the proliferation of LPS-stimulated B cells requires functional ion channels at a critical period in the G1 phase, taking place before transferrin receptor expression and the entry into the S phase [6].
• The Abeta 1-40 -8D3 conjugate is a bifunctional molecule that binds the blood-brain barrier TfR and undergoes transport into brain and binds the Abeta amyloid plaques of Alzheimer disease [7].

High impact information on Tfrc

• Furthermore, haploinsufficiency for Trfr results in impaired erythroid development and abnormal iron homeostasis [8].
• Mice lacking Trfr have a more severe phenotype than hpx mice, affecting both erythropoiesis and neurologic development [8].
• Transferrin receptor is necessary for development of erythrocytes and the nervous system [8].
• We also correlated the frequency of coated pits with the level of TR expression in different transfected L cell lines [9].
• These results indicate that the cytoplasmic domain plays an active role in sorting and endocytosis of TR by providing an assembly site for coated pit formation [9].

Chemical compound and disease context of Tfrc

• Differential expression of a Mr approximately 90,000 cell surface transferrin receptor-related glycoprotein on murine B16 metastatic melanoma sublines selected for enhanced brain or ovary colonization [10].
• Sodium ascorbate (vitamin C) induces apoptosis in melanoma cells via the down-regulation of transferrin receptor dependent iron uptake [11].
• In vitro and in vivo effect of HPMA copolymer-bound doxorubicin targeted to transferrin receptor of B-cell lymphoma 38C13 [12].
• We have investigated the structural and functional properties of the transferrin receptor from murine plasmacytoma cells (NS-1 cells) treated with the glycosylation inhibitor, tunicamycin and the glycosylation-processing inhibitors, swainsonine and castanospermine [13].
• Transgenic mice expressing the mutant TR displayed an mRNA expression pattern consistent with cardiac hypothyroidism, even though their peripheral thyroid hormone levels were normal [14].

Biological context of Tfrc

• Transferrin receptor (TfR) facilitates cellular iron uptake by mediating endocytosis of its ligand, iron-loaded transferrin [15].
• The high level of expression with our conjugate was confirmed using other tumor cells (M7609, TMK-1) whereas in normal diploid cells (HEL), which express low levels of Tf-R, expression was negligible [2].
• These data suggest that the down-regulation in IL-12 mRNA by anti-TfR mAb may prevent the development of T helper cells, thereby promoting graft survival and altering cell-mediated immune responses [16].
• The results suggest that the depletion of cellular non-heme iron due to the increase in heme synthesis maintains a high level of transferrin receptor expression in differentiating erythroid cells even after the cessation of cell division [17].
• TfR expression increased in the course of induction, as judged by increased TfR mRNA synthesis, increased cytoplasmic TfR mRNA level, and by the increased number of cellular 125I-Tf binding sites [17].

Anatomical context of Tfrc

• We conclude that a proportion of GLUT-4 is found in recycling endosomes in nonstimulated adipocytes together with cellubrevin and the transferrin receptor [18].
• Conversely, T cells lacking TfR are arrested very early in their development, at the CD4-8-3- stage [15].
• To elucidate the pathways by which nitric oxide (NO) influences macrophage iron metabolism, the uptake, release, and intracellular distribution of iron in the murine macrophage cell line J774 has been investigated, together with transferrin receptor (TfR) expression and iron-regulatory protein (IRP1 and IRP2) activity [19].
• These results indicate that TfR is necessary for the normal maturation of thymocytes, but that B-cell development is less severely affected by the absence of TfR [15].
• Transferrin receptor 1 is differentially required in lymphocyte development [15].

Associations of Tfrc with chemical compounds

• Common pathway for tumor cell uptake of gallium-67 and iron-59 via a transferrin receptor [20].
• According to this view, a tumor-associated TF receptor is the functional unit responsible for the affinity of gallium for certain neoplasms [20].
• Following direct acquisition of transferrin (Tf)-bound iron via the Tf receptor, iron uptake and release was equivalent in wild-type and mutant macrophages and was not influenced by interferon-gamma/lipopolysaccharide activation [21].
• SA had no effect on TfR expression in Fw cells [17].
• Comparison of the sequence with that of the human transferrin receptor shows a high degree of conservation of the sequences surrounding and penetrating the membrane, including cysteine residues that may be involved in interchain disulfide bonding and/or covalent attachment of lipid [22].

Physical interactions of Tfrc

• Transferrin transports iron into cells via the transferrin receptor: thus, iron content of resident cells is low, of peptone- and FCS-elicited cells is intermediate, and of thioglycollate-elicited cells is high [23].

Co-localisations of Tfrc

• Confocal microscopy using fluorescent anti-TCR mAb showed that after 15 min the TCR/CD3 complex colocalized with the transferrin receptor within endosomes, whereas at later times (2 h) it migrated in late endocytic compartments devoid of transferrin receptor [24].

Regulatory relationships of Tfrc

• Mice with targeted deletion of IRP2 overexpress ferritin and express abnormally low TfR levels in multiple tissues [25].
• MMTV-resistant human cells that expressed mouse transferrin receptor 1 became susceptible to MMTV infection, and treatment of mouse cells with a monoclonal antibody that down-regulated cell surface expression of the receptor blocked infection [26].
• The function of HFE protein is unknown, but it is hypothesized that it acts in association with beta(2)-microglobulin and transferrin receptor 1 to regulate iron uptake from plasma transferrin by the duodenum, the proposed mechanism by which body iron levels are sensed [27].
• Moreover, M-CSF regulated TfR and LDLR via the activation of distinct signaling pathways [28].
• Flow-cytometric studies revealed that HRCs obtained from Epo-injected mice expressed the transferrin receptor on their surface membranes [29].

Other interactions of Tfrc

• Coexpression of DMT1 and TfR in reticulocytes was also detected by double immunofluorescence and confocal microscopy [30].
• Significantly, we found that c-Tf is efficiently processed and presented when the TfR is cross-linked, altering its normal cycling [31].
• IRP2 downmodulation is associated with the upregulation of the ferritin L and H genes and decreased expression of the transferrin receptor 1 (TfR1) [32].
• This data suggests that IFN gamma may enhance iron uptake during the early phase of macrophage activation, and in later phases, down-regulate TfR expression by inducing NO, thus contributing to intracellular oxidative stress reduction [33].
• Finally, compound mutants lacking Hfe and the transferrin receptor accumulate more tissue iron than do mice lacking Hfe alone, consistent with the idea that interaction between these two proteins contributes to the control of normal iron absorption [34].

Analytical, diagnostic and therapeutic context of Tfrc

• Levels of the iron-related proteins TfR1, TfR2, ferritin, and prohepcidin were analyzed by immunoblotting [35].
• Anti-TfR mAb prolonged allograft survival to 25.7 +/- 0.9 days compared to the isotype control (10.7 +/- 0.4 days, P < 0.01, Wilcoxon rank sum) [16].
• Anti-TfR or isotype-matched control mAbs (100 microg) were administered at the time of transplantation and on the following day [16].
• I have investigated the distribution of the transferrin receptor in the adult mouse central nervous system by immunohistochemistry by using a monoclonal antibody raised against the transferrin receptor protein [36].
• We present deconvolution immunofluorescence microscopy data demonstrating that the subcellular distributions of ACRP30 and GLUT4 are distinct and nonoverlapping; in contrast, those of GLUT4 and the transferrin receptor overlap [37].

References