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Gene Review

Tf  -  transferrin

Rattus norvegicus

Synonyms: Beta-1 metal-binding globulin, Liver regeneration-related protein LRRG03, Serotransferrin, Siderophilin, Tfn, ...
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Disease relevance of Tf


Psychiatry related information on Tf


High impact information on Tf

  • The resialylated Tf accumulated in the extracellular medium with kinetics very similar to the time course for appearance of Tf in cholinesterase-containing, exocytic CVs, suggesting that these CVs are directly involved in the transfer of material from the trans Golgi to the cell surface [11].
  • We used a cholinesterase-mediated density shift protocol to investigate the movement of internalized transferrin (Tf) through endo- and exocytic coated vesicles (CVs) in the perfused rat liver [11].
  • In serum-free medium (1:1 mixture of DMEM:F-12) supplemented with insulin, hydrocortisone, transferrin and fibronectin (4F medium), the cells remained healthy and steroidogenically responsive for at least 60 days in culture [12].
  • In this study, the growth of rat follicular (RF-1) cells was severely depressed when the cells were subcultured by trypsinization directly into serum-free medium supplemented with insulin, transferrin and hydrocortisone, which are required for growth of these cells in vitro [13].
  • Iron unloading depends on the cycling of 24p3/Ngal through acidic endosomes, but its pH sensitivity and its subcellular targeting differed from transferrin [14].

Chemical compound and disease context of Tf


Biological context of Tf

  • Measurements of circulating transferrin (Tf) receptor are useful in assessing erythropoiesis; however, steps involved in the generation of soluble Tf receptor from cellular receptor are incompletely understood [20].
  • Current work showed up-regulation of Tf messenger RNA (mRNA) production in preneoplastic nodules, 12 to 37 weeks after initiation, and down-regulation in atypical nodules (at 45 and 50 weeks) and HCCs, induced in rats by the "resistant hepatocyte" model [3].
  • These findings suggested that Tf-Fe transport across the membrane of astrocytes is mediated by Tf-TfR endocytosis [21].
  • A single class of 125I-diferric Tf binding sites with an affinity constant of 1.65 x 10(7) l x l-1) and a capacity of 6.86 x 10(6) sites/cell was found [22].
  • This capacity may be associated with increased iron-Tf uptake from plasma, stabilization of TfR mRNA, or increased Tf mRNA translation efficiency in specific cell types within the brain [23].

Anatomical context of Tf


Associations of Tf with chemical compounds

  • OX26, the Fab fragment of OX26 (50K mol. wt.), and Tf complexed to two ferric ions were conjugated to HRP irreversibly in a 1:1 molar ratio [27].
  • The glucose-lowering effect of orally administered In-Tf in STZ-induced diabetic rats was improved by either T-8 or BFA [1].
  • PURPOSE: To investigate the effect of tyrphostin 8 (T-8), a GTPase inhibitor, on transferrin receptor (TfR)-mediated transcytosis of insulin-transferrin (In-Tf) conjugate in cultured enterocyte-like Caco-2 cells and on gastrointestinal (GI) absorption of In-Tf in streptozotocin (STZ)-induced diabetic rats [1].
  • The GI absorption of In-Tf was evaluated by its hypoglycemic effect after oral administration in STZ-induced diabetic rats [1].
  • Preincubation of hepatocytes with the low-M(r) Fe complex ferric ammonium citrate (FAC; 25 microg/mL; (Fe) = 4.4 microg/mL) followed by incubation with 59Fe-Tf or 59Fe-citrate ((Fe) = 0.25 to 25 micromol/L) resulted in the marked stimulation of 59Fe uptake [5].

Physical interactions of Tf


Co-localisations of Tf


Regulatory relationships of Tf


Other interactions of Tf

  • The cultured rat astrocytes were incubated with 1 microM of double-labelled transferrin (125I-Tf-59Fe) in serum- free DMEM F12 medium or 59Fe II in isotonic sucrose solution at 37 degrees C or 4 degrees C for varying times [21].
  • The aim of this study was to determine whether the gene for Tf was activated in specific lung cells during development, and whether the protein product showed evidence of association with extracellular matrix [41].
  • Our results indicate that this conjugate binds to Tf receptors on the luminal BBB, is internalized via clathrin-coated vesicles, enters early or sorting endosomes, and, subsequently, late or recycling endosomes near the Golgi apparatus [42].
  • Based on preliminary immunofluorescence observations, we had suggested that synaptophysin is targeted to the preexisting population of microvesicles that recycle transferrin (Johnston, P. A., P. L. Cameron, H. Stukenbrok, R. Jahn, P. De Camilli, and T. C. Südhof. 1989. EMBO (Eur. Mol. Biol. Organ.) J. 8:2863-2872) [43].
  • This redistribution of transferrin receptors between cellular membrane fractions in response to insulin is remarkably similar to the regulation by insulin of glucose transporters and type II insulin-like growth factor receptors [44].

Analytical, diagnostic and therapeutic context of Tf


  1. Tyrphostin-8 enhances transferrin receptor-mediated transcytosis in Caco-2- cells and inreases hypoglycemic effect of orally administered insulin-transferrin conjugate in diabetic rats. Xia, C.Q., Shen, W.C. Pharm. Res. (2001) [Pubmed]
  2. Thrombin preconditioning upregulates transferrin and transferrin receptor and reduces brain edema induced by lysed red blood cells. Xi, G., Wu, J., Jiang, Y., Hua, Y., Keep, R.F., Hoff, J.T. Acta Neurochir. Suppl. (2003) [Pubmed]
  3. Transferrin and transferrin receptor gene expression and iron uptake in hepatocellular carcinoma in the rat. Pascale, R.M., De Miglio, M.R., Muroni, M.R., Simile, M.M., Daino, L., Seddaiu, M.A., Pusceddu, S., Gaspa, L., Calvisi, D., Manenti, G., Feo, F. Hepatology (1998) [Pubmed]
  4. Variable tissue expression of transferrin receptors: relevance to acute respiratory distress syndrome. Upton, R.L., Chen, Y., Mumby, S., Gutteridge, J.M., Anning, P.B., Nicholson, A.G., Evans, T.W., Quinlan, G.J. Eur. Respir. J. (2003) [Pubmed]
  5. Activation of an iron uptake mechanism from transferrin in hepatocytes by small-molecular-weight iron complexes: implications for the pathogenesis of iron-overload disease. Richardson, D.R., Chua, A.C., Baker, E. J. Lab. Clin. Med. (1999) [Pubmed]
  6. Transferrin receptors of rat and human brain and cerebral microvessels and their status in Alzheimer's disease. Kalaria, R.N., Sromek, S.M., Grahovac, I., Harik, S.I. Brain Res. (1992) [Pubmed]
  7. Role of basic-helix-loop-helix transcription factors in Sertoli cell differentiation: identification of an E-box response element in the transferrin promoter. Chaudhary, J., Cupp, A.S., Skinner, M.K. Endocrinology (1997) [Pubmed]
  8. Effects of chronic ethanol on enzymes regulating sialylation and desialylation of transferrin in rats. Ghosh, P., Okoh, C., Liu, Q.H., Lakshman, M.R. Alcohol. Clin. Exp. Res. (1993) [Pubmed]
  9. Magnocellular neurosecretory neurons with ferritin-like immunoreactivity in the hypothalamic supraoptic and paraventricular nuclei of the rat. Tokunaga, A., Ono, K., Ono, T., Ogawa, M. Brain Res. (1992) [Pubmed]
  10. Transferrin glycans: a possible link between alcoholism and hepatic siderosis. Regoeczi, E., Chindemi, P.A., Debanne, M.T. Alcohol. Clin. Exp. Res. (1984) [Pubmed]
  11. A trans Golgi-derived exocytic coated vesicle can contain both newly synthesized cholinesterase and internalized transferrin. Fishman, J.B., Fine, R.E. Cell (1987) [Pubmed]
  12. Serum suppresses the expression of hormonally induced functions in cultured granulosa cells. Orly, J., Sato, G., Erickson, G.F. Cell (1980) [Pubmed]
  13. Fibronectin mediates cytokinesis and growth of rat follicular cells in serum-free medium. Orly, J., Sato, G. Cell (1979) [Pubmed]
  14. An iron delivery pathway mediated by a lipocalin. Yang, J., Goetz, D., Li, J.Y., Wang, W., Mori, K., Setlik, D., Du, T., Erdjument-Bromage, H., Tempst, P., Strong, R., Barasch, J. Mol. Cell (2002) [Pubmed]
  15. Evidence for in vivo expression of transferrin-binding proteins in Haemophilus influenzae type b. Holland, J., Langford, P.R., Towner, K.J., Williams, P. Infect. Immun. (1992) [Pubmed]
  16. Targeted drug delivery to C6 glioma by transferrin-coupled liposomes. Eavarone, D.A., Yu, X., Bellamkonda, R.V. J. Biomed. Mater. Res. (2000) [Pubmed]
  17. Changes in function of iron-loaded alveolar macrophages after in vivo administration of desferrioxamine and/or chloroquine. Legssyer, R., Josse, C., Piette, J., Ward, R.J., Crichton, R.R. J. Inorg. Biochem. (2003) [Pubmed]
  18. Growth of a rat neuroblastoma cell line in serum-free supplemented medium. Bottenstein, J.E., Sato, G.H. Proc. Natl. Acad. Sci. U.S.A. (1979) [Pubmed]
  19. Intestinal absorption and enterohepatic cycling of biliary iron originating from plasma non-transferrin-bound iron in rats. Brissot, P., Bolder, U., Schteingart, C.D., Arnaud, J., Hofmann, A.F. Hepatology (1997) [Pubmed]
  20. Shedding of transferrin receptor from rat reticulocytes during maturation in vitro: soluble transferrin receptor is derived from receptor shed in vesicles. Chitambar, C.R., Loebel, A.L., Noble, N.A. Blood (1991) [Pubmed]
  21. Transferrin-bound and transferrin free iron uptake by cultured rat astrocytes. Qian, Z.M., Liao, Q.K., To, Y., Ke, Y., Tsoi, Y.K., Wang, G.F., Ho, K.P. Cell. Mol. Biol. (Noisy-le-grand) (2000) [Pubmed]
  22. Transferrin receptor on rat Kupffer cells in primary culture. Kumazawa, M., Misaki, M., Baba, M., Shima, T., Suzuki, S. Liver (1986) [Pubmed]
  23. Gene expression of transferrin and transferrin receptor in brains of control vs. iron-deficient rats. Han, J., Day, J.R., Connor, J.R., Beard, J.L. Nutritional neuroscience. (2003) [Pubmed]
  24. Iron, ferritin, transferrin, and transferrin receptor in the adult rat retina. Yefimova, M.G., Jeanny, J.C., Guillonneau, X., Keller, N., Nguyen-Legros, J., Sergeant, C., Guillou, F., Courtois, Y. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
  25. Impaired retinal iron homeostasis associated with defective phagocytosis in Royal College of Surgeons rats. Yefimova, M.G., Jeanny, J.C., Keller, N., Sergeant, C., Guillonneau, X., Beaumont, C., Courtois, Y. Invest. Ophthalmol. Vis. Sci. (2002) [Pubmed]
  26. Manganese and iron transport across pulmonary epithelium. Heilig, E.A., Thompson, K.J., Molina, R.M., Ivanov, A.R., Brain, J.D., Wessling-Resnick, M. Am. J. Physiol. Lung Cell Mol. Physiol. (2006) [Pubmed]
  27. Transcytosis of protein through the mammalian cerebral epithelium and endothelium. III. Receptor-mediated transcytosis through the blood-brain barrier of blood-borne transferrin and antibody against the transferrin receptor. Broadwell, R.D., Baker-Cairns, B.J., Friden, P.M., Oliver, C., Villegas, J.C. Exp. Neurol. (1996) [Pubmed]
  28. Transferrin receptors in rat plasma. Beguin, Y., Huebers, H.A., Josephson, B., Finch, C.A. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  29. The entering of indium-111 and iron-59 into the hepatocytes from partially hepatectomized rats differ from that of gallium-67. Sato, R., Abe, S., Yamada, Y., Toyama, D., Ohtake, Y., Sato, N., Ohkubo, Y. Biol. Pharm. Bull. (2004) [Pubmed]
  30. Role of basic helix-loop-helix (bHLH) and CREB transcription factors in the regulation of Sertoli cell androgen-binding protein expression. Saxlund, M.A., Sadler-Riggleman, I., Skinner, M.K. Mol. Reprod. Dev. (2004) [Pubmed]
  31. The effect of cocaine and its metabolites on Sertoli cell function. Zhang, H., Loughlin, K.R. J. Urol. (1996) [Pubmed]
  32. Intracellular forms of transferrin oligosaccharide chains in rat liver. Nakada, H., Kohno, H., Kawasaki, T., Tashiro, Y. Eur. J. Biochem. (1983) [Pubmed]
  33. Synaptophysin is targeted to similar microvesicles in CHO and PC12 cells. Johnston, P.A., Cameron, P.L., Stukenbrok, H., Jahn, R., De Camilli, P., Südhof, T.C. EMBO J. (1989) [Pubmed]
  34. Developmental patterns of gene expression of secreted proteins in brain and choroid plexus. Thomas, T., Schreiber, G., Jaworowski, A. Dev. Biol. (1989) [Pubmed]
  35. Retention and stimulus-dependent recycling of dense core vesicle content in neuroendocrine cells. Bauer, R.A., Overlease, R.L., Lieber, J.L., Angleson, J.K. J. Cell. Sci. (2004) [Pubmed]
  36. Ligand-induced internalization of the p75 neurotrophin receptor: a slow route to the signaling endosome. Bronfman, F.C., Tcherpakov, M., Jovin, T.M., Fainzilber, M. J. Neurosci. (2003) [Pubmed]
  37. Calmodulin antagonists inhibit and phorbol esters enhance transferrin endocytosis and iron uptake by immature erythroid cells. Hebbert, D., Morgan, E.H. Blood (1985) [Pubmed]
  38. Liver-regulating protein (LRP) is a plasma membrane protein involved in cell contact-mediated regulation of Sertoli cell function by primary spermatocytes. Gérard, N., Corlu, A., Kneip, B., Kercret, H., Rissel, M., Guguen-Guillouzo, C., Jégou, B. J. Cell. Sci. (1995) [Pubmed]
  39. Transferrin inhibits aromatase activity of rat granulosa cells in vitro. Li, Y.D., Zhang, Z.W., Li, W.X. J. Endocrinol. (1991) [Pubmed]
  40. Multiplication stimulating activity (MSA) can substitute for insulin to stimulate the secretion of testicular transferrin by cultured Sertoli cells. Skinner, M.K., Griswold, M.D. Cell Biol. Int. Rep. (1983) [Pubmed]
  41. Transferrin gene expression and transferrin immunolocalization in developing foetal rat lung. Skinner, S.J., Somervell, C.E., Buch, S., Post, M. J. Cell. Sci. (1991) [Pubmed]
  42. Studies of the mechanism of iron transport across the blood-brain barrier. Roberts, R., Sandra, A., Siek, G.C., Lucas, J.J., Fine, R.E. Ann. Neurol. (1992) [Pubmed]
  43. Colocalization of synaptophysin with transferrin receptors: implications for synaptic vesicle biogenesis. Cameron, P.L., Südhof, T.C., Jahn, R., De Camilli, P. J. Cell Biol. (1991) [Pubmed]
  44. Insulin stimulates cellular iron uptake and causes the redistribution of intracellular transferrin receptors to the plasma membrane. Davis, R.J., Corvera, S., Czech, M.P. J. Biol. Chem. (1986) [Pubmed]
  45. Thrombin preconditioning attenuates brain edema induced by erythrocytes and iron. Hua, Y., Keep, R.F., Hoff, J.T., Xi, G. J. Cereb. Blood Flow Metab. (2003) [Pubmed]
  46. Transferrin receptor gene expression and transferrin-bound iron uptake are increased during postischemic rat liver reperfusion. Tacchini, L., Fusar Poli, D., Bernelli-Zazzera, A., Cairo, G. Hepatology (2002) [Pubmed]
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