1932

Abstract

Because both the host and pathogen require iron, the innate immune response carefully orchestrates control over iron metabolism to limit its availability during times of infection. Nutritional iron deficiency can impair host immunity, while iron overload can cause oxidative stress to propagate harmful viral mutations. An emerging enigma is that many viruses use the primary gatekeeper of iron metabolism, the transferrin receptor, as a means to enter cells. Why and how this iron gate is a viral target for infection are the focus of this review.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-nutr-082117-051749
2018-08-21
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/nutr/38/1/annurev-nutr-082117-051749.html?itemId=/content/journals/10.1146/annurev-nutr-082117-051749&mimeType=html&fmt=ahah

Literature Cited

  1. 1.  Abraham J, Corbett KD, Farzan M, Choe H, Harrison SC 2010. Structural basis for receptor recognition by New World hemorrhagic fever arenaviruses. Nat. Struct. Mol. Biol. 17:438–44
    [Google Scholar]
  2. 2.  Ajioka RS, Kaplan J 1986. Intracellular pools of transferrin receptors result from constitutive internalization of unoccupied receptors. PNAS 83:6445–49
    [Google Scholar]
  3. 3.  Alkhouri N, Lawitz E, Poordad F 2017. Novel treatments for chronic hepatitis C: closing the remaining gaps. Curr. Opin. Pharmacol. 37:107–11
    [Google Scholar]
  4. 4.  Andrews NC 2008. Forging a field: the golden age of iron biology. Blood 112:219–30
    [Google Scholar]
  5. 5.  Armitage AE, Stacey AR, Giannoulatou E, Marshall E, Sturges P et al. 2014. Distinct patterns of hepcidin and iron regulation during HIV-1, HBV, and HCV infections. PNAS 111:12187–92
    [Google Scholar]
  6. 6.  Asano T, Komatsu M, Yamaguchi-Iwai Y, Ishikawa F, Mizushima N, Iwai K 2011. Distinct mechanisms of ferritin delivery to lysosomes in iron-depleted and iron-replete cells. Mol. Cell. Biol. 31:2040–52
    [Google Scholar]
  7. 7.  Babitt JL, Huang FW, Wrighting DM, Xia Y, Sidis Y et al. 2006. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat. Genet. 38:531–39
    [Google Scholar]
  8. 8.  Barrientos T, Laothamatas I, Koves TR, Soderblom EJ, Bryan M et al. 2015. Metabolic catastrophe in mice lacking transferrin receptor in muscle. EBioMedicine 2:1705–17
    [Google Scholar]
  9. 9.  Bartnikas TB 2012. Known and potential roles of transferrin in iron biology. BioMetals 25:677–86
    [Google Scholar]
  10. 10.  Batista A, Millan J, Mittelbrunn M, Sanchez-Madrid F, Alonso MA 2004. Recruitment of transferrin receptor to immunological synapse in response to TCR engagement. J. Immunol. 172:6709–14
    [Google Scholar]
  11. 11.  Bayeva M, Khechaduri A, Puig S, Chang HC, Patial S et al. 2012. mTOR regulates cellular iron homeostasis through tristetraprolin. Cell Metab 16:645–57
    [Google Scholar]
  12. 12.  Beck MA 2007. Selenium and vitamin E status: impact on viral pathogenicity. J. Nutr. 137:1338–40
    [Google Scholar]
  13. 13.  Beck MA, Handy J, Levander OA 2004. Host nutritional status: the neglected virulence factor. Trends Microbiol 12:417–23
    [Google Scholar]
  14. 14.  Bellelli R, Federico G, Matte A, Colecchia D, Iolascon A et al. 2016. NCOA4 deficiency impairs systemic iron homeostasis. Cell Rep 14:411–21
    [Google Scholar]
  15. 15.  Boshuizen M, van der Ploeg K, von Bonsdorff L, Biemond BJ, Zeerleder SS et al. 2017. Therapeutic use of transferrin to modulate anemia and conditions of iron toxicity. Blood Rev 31:400–5
    [Google Scholar]
  16. 16.  Bowden TA, Crispin M, Graham SC, Harvey DJ, Grimes JM et al. 2009. Unusual molecular architecture of the Machupo virus attachment glycoprotein. J. Virol. 83:8259–65
    [Google Scholar]
  17. 17.  Buchkovich NJ, Yu Y, Zampieri CA, Alwine JC 2008. The TORrid affairs of viruses: effects of mammalian DNA viruses on the PI3K-Akt-mTOR signalling pathway. Nat. Rev. Microbiol. 6:266–75
    [Google Scholar]
  18. 18.  Byrne SL, Buckett PD, Kim J, Luo F, Sanford J et al. 2013. Ferristatin II promotes degradation of transferrin receptor-1 in vitro and in vivo. PLOS ONE 8:e70199
    [Google Scholar]
  19. 19.  Camaschella C 2015. Iron-deficiency anemia. N. Engl. J. Med. 373:485–86
    [Google Scholar]
  20. 20.  Camaschella C, Roetto A, Cali A, De Gobbi M Garozzo G et al. 2000. The gene TFR2 is mutated in a new type of haemochromatosis mapping to 7q22. Nat. Genet. 25:14–15
    [Google Scholar]
  21. 21.  Cao H, Chen J, Krueger EW, McNiven MA 2010. Src-mediated phosphorylation of dynamin and cortactin regulates the “constitutive” endocytosis of transferrin. Mol. Cell. Biol. 30:781–92
    [Google Scholar]
  22. 22.  Castilla V, Mersich SE 1996. Low-pH-induced fusion of Vero cells infected with Junin virus. Arch. Virol. 141:1307–17
    [Google Scholar]
  23. 23.  Chen AC, Donovan A, Ned-Sykes R, Andrews NC 2015. Noncanonical role of transferrin receptor 1 is essential for intestinal homeostasis. PNAS 112:11714–19
    [Google Scholar]
  24. 24.  Chen C, Garcia-Santos D, Ishikawa Y, Seguin A, Li L et al. 2013. Snx3 regulates recycling of the transferrin receptor and iron assimilation. Cell Metab 17:343–52
    [Google Scholar]
  25. 25.  Chen J, Chloupkova M, Gao J, Chapman-Arvedson TL, Enns CA 2007. HFE modulates transferrin receptor 2 levels in hepatoma cells via interactions that differ from transferrin receptor 1–HFE interactions. J. Biol. Chem. 282:36862–70
    [Google Scholar]
  26. 26.  Christoforidis S, McBride HM, Burgoyne RD, Zerial M 1999. The Rab5 effector EEA1 is a core component of endosome docking. Nature 397:621–25
    [Google Scholar]
  27. 27.  Chua AC, Herbison CE, Drake SF, Graham RM, Olynyk JK, Trinder D 2008. The role of Hfe in transferrin-bound iron uptake by hepatocytes. Hepatology 47:1737–44
    [Google Scholar]
  28. 28.  Coffin JM 2013. Virions at the gates: receptors and the host–virus arms race. PLOS Biol 11:e1001574
    [Google Scholar]
  29. 29.  Collawn JF, Lai A, Domingo D, Fitch M, Hatton S, Trowbridge IS 1993. YTRF is the conserved internalization signal of the transferrin receptor, and a second YTRF signal at position 31–34 enhances endocytosis. J. Biol. Chem. 268:21686–92
    [Google Scholar]
  30. 30.  Conner SD, Schmid SL 2003. Regulated portals of entry into the cell. Nature 422:37–44
    [Google Scholar]
  31. 31.  Cullen PJ 2008. Endosomal sorting and signalling: an emerging role for sorting nexins. Nat. Rev. Mol. Cell Biol. 9:574–82
    [Google Scholar]
  32. 32.  Cureton DK, Harbison CE, Cocucci E, Parrish CR, Kirchhausen T 2012. Limited transferrin receptor clustering allows rapid diffusion of canine parvovirus into clathrin endocytic structures. J. Virol. 86:5330–40
    [Google Scholar]
  33. 33.  D'Alessio F, Hentze MW, Muckenthaler MU 2012. The hemochromatosis proteins HFE, TfR2, and HJV form a membrane-associated protein complex for hepcidin regulation. J. Hepatol. 57:1052–60
    [Google Scholar]
  34. 34.  Dale JC, Burritt MF, Zinsmeister AR 2002. Diurnal variation of serum iron, iron-binding capacity, transferrin saturation, and ferritin levels. Am. J. Clin. Pathol. 117:802–8
    [Google Scholar]
  35. 35.  Dauner K, Eid W, Raghupathy R, Presley JF, Zha X 2017. mTOR complex 1 activity is required to maintain the canonical endocytic recycling pathway against lysosomal delivery. J. Biol. Chem. 292:5737–47
    [Google Scholar]
  36. 36.  Dautry-Varsat A, Ciechanover A, Lodish HF 1983. pH and the recycling of transferrin during receptor-mediated endocytosis. PNAS 80:2258–62
    [Google Scholar]
  37. 37.  Demogines A, Abraham J, Choe H, Farzan M, Sawyer SL 2013. Dual host–virus arms races shape an essential housekeeping protein. PLOS Biol 11:e1001571
    [Google Scholar]
  38. 38.  Di Bisceglie AM, Axiotis CA, Hoofnagle JH, Bacon BR 1992. Measurements of iron status in patients with chronic hepatitis. Gastroenterology 102:2108–13
    [Google Scholar]
  39. 39.  Di Paolo G, De Camilli P 2006. Phosphoinositides in cell regulation and membrane dynamics. Nature 443:651–57
    [Google Scholar]
  40. 40.  Dibble CC, Manning BD 2013. Signal integration by mTORC1 coordinates nutrient input with biosynthetic output. Nat. Cell Biol. 15:555–64
    [Google Scholar]
  41. 41.  Dowdle WE, Nyfeler B, Nagel J, Elling RA, Liu S et al. 2014. Selective VPS34 inhibitor blocks autophagy and uncovers a role for NCOA4 in ferritin degradation and iron homeostasis in vivo. Nat. Cell Biol. 16:1069–79
    [Google Scholar]
  42. 42.  Drakesmith H, Chen N, Ledermann H, Screaton G, Townsend A, Xu XN 2005. HIV-1 Nef down-regulates the hemochromatosis protein HFE, manipulating cellular iron homeostasis. PNAS 102:11017–22
    [Google Scholar]
  43. 43.  Drakesmith H, Prentice AM 2012. Hepcidin and the iron-infection axis. Science 338:768–72
    [Google Scholar]
  44. 44.  Eckenroth BE, Steere AN, Chasteen ND, Everse SJ, Mason AB 2011. How the binding of human transferrin primes the transferrin receptor potentiating iron release at endosomal pH. PNAS 108:13089–94
    [Google Scholar]
  45. 45.  Eggers CT, Schafer JC, Goldenring JR, Taylor SS 2009. D-AKAP2 interacts with Rab4 and Rab11 through its RGS domains and regulates transferrin receptor recycling. J. Biol. Chem. 284:32869–80
    [Google Scholar]
  46. 46.  Ehrlich M, Boll W, Van Oijen A, Hariharan R, Chandran K et al. 2004. Endocytosis by random initiation and stabilization of clathrin-coated pits. Cell 118:591–605
    [Google Scholar]
  47. 47.  Ekiz C, Agaoglu L, Karakas Z, Gurel N, Yalcin I 2005. The effect of iron deficiency anemia on the function of the immune system. Hematol. J. 5:579–83
    [Google Scholar]
  48. 48.  Farci P, Shimoda A, Coiana A, Diaz G, Peddis G et al. 2000. The outcome of acute hepatitis C predicted by the evolution of the viral quasispecies. Science 288:339–44
    [Google Scholar]
  49. 49.  Feder JN, Gnirke A, Thomas W, Tsuchihashi Z, Ruddy DA et al. 1996. A novel MHC class I–like gene is mutated in patients with hereditary haemochromatosis. Nat. Genet. 13:399–408
    [Google Scholar]
  50. 50.  Fillebeen C, Pantopoulos K 2013. Hepatitis C virus infection causes iron deficiency in Huh7.5.1 cells. PLOS ONE 8:e83307
    [Google Scholar]
  51. 51.  Fleming RE, Ahmann JR, Migas MC, Waheed A, Koeffler HP et al. 2002. Targeted mutagenesis of the murine transferrin receptor-2 gene produces hemochromatosis. PNAS 99:10653–58
    [Google Scholar]
  52. 52.  Foster JL, Garcia JV 2008. HIV-1 Nef: at the crossroads. Retrovirology 5:84
    [Google Scholar]
  53. 53.  Frazer DM, Anderson GJ 2014. The regulation of iron transport. BioFactors 40:206–14
    [Google Scholar]
  54. 54.  Freeze HH 2013. Understanding human glycosylation disorders: Biochemistry leads the charge. J. Biol. Chem. 288:6936–45
    [Google Scholar]
  55. 55.  Fujita H, Iwabu Y, Tokunaga K, Tanaka Y 2013. Membrane-associated RING-CH (MARCH) 8 mediates the ubiquitination and lysosomal degradation of the transferrin receptor. J. Cell Sci. 126:2798–809
    [Google Scholar]
  56. 56.  Fujita N, Sugimoto R, Takeo M, Urawa N, Mifuji R et al. 2007. Hepcidin expression in the liver: relatively low level in patients with chronic hepatitis C. Mol. Med. 13:97–104
    [Google Scholar]
  57. 57.  Fujita N, Sugimoto R, Urawa N, Araki J, Mifuji R et al. 2007. Hepatic iron accumulation is associated with disease progression and resistance to interferon/ribavirin combination therapy in chronic hepatitis C. J. Gastroenterol. Hepatol. 22:1886–93
    [Google Scholar]
  58. 58.  Fujita N, Takei Y 2007. Iron, hepatitis C virus, and hepatocellular carcinoma: Iron reduction preaches the gospel for chronic hepatitis C. J. Gastroenterol. 42:923–26
    [Google Scholar]
  59. 59.  Galvez T, Teruel MN, Heo WD, Jones JT, Kim ML et al. 2007. siRNA screen of the human signaling proteome identifies the PtdIns(3,4,5)P3-mTOR signaling pathway as a primary regulator of transferrin uptake. Genome Biol 8:R142
    [Google Scholar]
  60. 60.  Ganz T 2013. Systemic iron homeostasis. Physiol. Rev. 93:1721–41
    [Google Scholar]
  61. 61.  Gao J, Chen J, Kramer M, Tsukamoto H, Zhang AS, Enns CA 2009. Interaction of the hereditary hemochromatosis protein HFE with transferrin receptor 2 is required for transferrin-induced hepcidin expression. Cell Metab 9:217–27
    [Google Scholar]
  62. 62.  Garrick MD, Garrick LM 2007. Loss of rapid transferrin receptor recycling due to a mutation in Sec15l1 in hbd mice. Biochim. Biophys. Acta 1773:105–8
    [Google Scholar]
  63. 63.  Gaudin R, Kirchhausen T 2015. Superinfection exclusion is absent during acute Junin virus infection of Vero and A549 cells. Sci. Rep. 5:15990
    [Google Scholar]
  64. 64.  Giannetti AM, Bjorkman PJ 2004. HFE and transferrin directly compete for transferrin receptor in solution and at the cell surface. J. Biol. Chem. 279:25866–75
    [Google Scholar]
  65. 65.  Giannetti AM, Snow PM, Zak O, Bjorkman PJ 2003. Mechanism for multiple ligand recognition by the human transferrin receptor. PLOS Biol 1:e51
    [Google Scholar]
  66. 66.  Girelli D, Trombini P, Busti F, Campostrini N, Sandri M et al. 2011. A time course of hepcidin response to iron challenge in patients with HFE and TFR2 hemochromatosis. Haematologica 96:500–6
    [Google Scholar]
  67. 67.  Girones N, Davis RJ 1989. Comparison of the kinetics of cycling of the transferrin receptor in the presence or absence of bound diferric transferrin. Biochem. J. 264:35–46
    [Google Scholar]
  68. 68.  Gkouvatsos K, Papanikolaou G, Pantopoulos K 2012. Regulation of iron transport and the role of transferrin. Biochim. Biophys. Acta 1820:188–202
    [Google Scholar]
  69. 69.  Goodman LB, Lyi SM, Johnson NC, Cifuente JO, Hafenstein SL, Parrish CR 2010. Binding site on the transferrin receptor for the parvovirus capsid and effects of altered affinity on cell uptake and infection. J. Virol. 84:4969–78
    [Google Scholar]
  70. 70.  Goswami T, Andrews NC 2006. Hereditary hemochromatosis protein, HFE, interaction with transferrin receptor 2 suggests a molecular mechanism for mammalian iron sensing. J. Biol. Chem. 281:28494–98
    [Google Scholar]
  71. 71.  Guan P, Wang N 2014. Mammalian target of rapamycin coordinates iron metabolism with iron–sulfur cluster assembly enzyme and tristetraprolin. Nutrition 30:968–74
    [Google Scholar]
  72. 72.  Hafenstein S, Palermo LM, Kostyuchenko VA, Xiao C, Morais MC et al. 2007. Asymmetric binding of transferrin receptor to parvovirus capsids. PNAS 104:6585–89
    [Google Scholar]
  73. 73.  Harold D, Abraham R, Hollingworth P, Sims R, Gerrish A et al. 2009. Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease. Nat. Genet. 41:1088–93
    [Google Scholar]
  74. 74.  Helguera G, Jemielity S, Abraham J, Cordo SM, Martinez MG et al. 2012. An antibody recognizing the apical domain of human transferrin receptor 1 efficiently inhibits the entry of all New World hemorrhagic fever arenaviruses. J. Virol. 86:4024–28
    [Google Scholar]
  75. 75.  Hentze MW, Muckenthaler MU, Andrews NC 2004. Balancing acts: molecular control of mammalian iron metabolism. Cell 117:285–97
    [Google Scholar]
  76. 76.  Horonchik L, Wessling-Resnick M 2008. The small-molecule iron transport inhibitor ferristatin/NSC306711 promotes degradation of the transferrin receptor. Chem. Biol. 15:647–53
    [Google Scholar]
  77. 77.  Hueffer K, Parker JS, Weichert WS, Geisel RE, Sgro JY, Parrish CR 2003. The natural host range shift and subsequent evolution of canine parvovirus resulted from virus-specific binding to the canine transferrin receptor. J. Virol. 77:1718–26
    [Google Scholar]
  78. 78.  Iacopetta BJ, Morgan EH, Yeoh GC 1982. Transferrin receptors and iron uptake during erythroid cell development. Biochim. Biophys. Acta 687:204–10
    [Google Scholar]
  79. 79.  Isanaka S, Mugusi F, Urassa W, Willett WC, Bosch RJ et al. 2012. Iron deficiency and anemia predict mortality in patients with tuberculosis. J. Nutr. 142:350–57
    [Google Scholar]
  80. 80.  Ishikawa Y, Maeda M, Pasham M, Aguet F, Tacheva-Grigorova SK et al. 2015. Role of the clathrin adaptor PICALM in normal hematopoiesis and polycythemia vera pathophysiology. Haematologica 100:439–51
    [Google Scholar]
  81. 81.  Jabara HH, Boyden SE, Chou J, Ramesh N, Massaad MJ et al. 2016. A missense mutation in TFRC, encoding transferrin receptor 1, causes combined immunodeficiency. Nat. Genet. 48:74–78
    [Google Scholar]
  82. 82.  Jain A, Chasoo G, Singh SK, Saxena AK, Jain SK 2011. Transferrin-appended PEGylated nanoparticles for temozolomide delivery to brain: in vitro characterisation. J. Microencapsul. 28:21–28
    [Google Scholar]
  83. 83.  Johannes L, Wunder C 2011. Retrograde transport: Two (or more) roads diverged in an endosomal tree?. Traffic 12:956–62
    [Google Scholar]
  84. 84.  Johnson MB, Enns CA 2004. Diferric transferrin regulates transferrin receptor 2 protein stability. Blood 104:4287–93
    [Google Scholar]
  85. 85.  Joung I, Harber G, Gerecke KM, Carroll SL, Collawn JF, Engler JA 2005. Improved gene delivery into neuroglial cells using a fiber-modified adenovirus vector. Biochem. Biophys. Res. Commun. 328:1182–87
    [Google Scholar]
  86. 86.  Kaelber JT, Demogines A, Harbison CE, Allison AB, Goodman LB et al. 2012. Evolutionary reconstructions of the transferrin receptor of caniforms supports canine parvovirus being a re-emerged and not a novel pathogen in dogs. PLOS Pathog 8:e1002666
    [Google Scholar]
  87. 87.  Kaito M 2007. Molecular mechanism of iron metabolism and overload in chronic hepatitis C. J. Gastroenterol. 42:96–99
    [Google Scholar]
  88. 88.  Kawabata H, Tong X, Kawanami T, Wano Y, Hirose Y et al. 2004. Analyses for binding of the transferrin family of proteins to the transferrin receptor 2. Br. J. Haematol. 127:464–73
    [Google Scholar]
  89. 89.  Kawabata H, Yang R, Hirama T, Vuong PT, Kawano S et al. 1999. Molecular cloning of transferrin receptor 2: a new member of the transferrin receptor–like family. J. Biol. Chem. 274:20826–32
    [Google Scholar]
  90. 90.  Kenneth NS, Mudie S, Naron S, Rocha S 2013. TfR1 interacts with the IKK complex and is involved in IKK–NF-κB signalling. Biochem. J. 449:275–84
    [Google Scholar]
  91. 91.  Kielian M, Chanel-Vos C, Liao M 2010. Alphavirus entry and membrane fusion. Viruses 2:796–825
    [Google Scholar]
  92. 92.  Kirchhausen T, Owen D, Harrison SC 2014. Molecular structure, function, and dynamics of clathrin-mediated membrane traffic. Cold Spring Harb. Perspect. Biol. 6:a016725
    [Google Scholar]
  93. 93.  Klausner RD, Ashwell G, van Renswoude J, Harford JB, Bridges KR 1983. Binding of apotransferrin to K562 cells: explanation of the transferrin cycle. PNAS 80:2263–66
    [Google Scholar]
  94. 94.  Koppensteiner H, Hohne K, Gondim MV, Gobert FX, Widder M et al. 2014. Lentiviral Nef suppresses iron uptake in a strain specific manner through inhibition of Transferrin endocytosis. Retrovirology 11:1
    [Google Scholar]
  95. 95.  Kupka R, Msamanga GI, Mugusi F, Petraro P, Hunter DJ, Fawzi WW 2007. Iron status is an important cause of anemia in HIV-infected Tanzanian women but is not related to accelerated HIV disease progression. J. Nutr. 137:2317–23
    [Google Scholar]
  96. 96.  Lambert LA 2012. Molecular evolution of the transferrin family and associated receptors. Biochim. Biophys. Acta 1820:244–55
    [Google Scholar]
  97. 97.  Lawrence CM, Ray S, Babyonyshev M, Galluser R, Borhani DW, Harrison SC 1999. Crystal structure of the ectodomain of human transferrin receptor. Science 286:779–82
    [Google Scholar]
  98. 98.  Lei R, Zhang K, Liu K, Shao X, Ding Z et al. 2016. Transferrin receptor facilitates TGF-β and BMP signaling activation to control craniofacial morphogenesis. Cell Death Dis 7:e2282
    [Google Scholar]
  99. 99.  Leverence R, Mason AB, Kaltashov IA 2010. Noncanonical interactions between serum transferrin and transferrin receptor evaluated with electrospray ionization mass spectrometry. PNAS 107:8123–28
    [Google Scholar]
  100. 100.  Levy JE, Jin O, Fujiwara Y, Kuo F, Andrews NC 1999. Transferrin receptor is necessary for development of erythrocytes and the nervous system. Nat. Genet. 21:396–99
    [Google Scholar]
  101. 101.  Li L, Fang CJ, Ryan JC, Niemi EC, Lebron JA et al. 2010. Binding and uptake of H-ferritin are mediated by human transferrin receptor-1. PNAS 107:3505–10
    [Google Scholar]
  102. 102.  Lim JE, Jin O, Bennett C, Morgan K, Wang F et al. 2005. A mutation in Sec15l1 causes anemia in hemoglobin deficit (hbd) mice. Nat. Genet. 37:1270–73
    [Google Scholar]
  103. 103.  Lucas M, Gershlick DC, Vidaurrazaga A, Rojas AL, Bonifacino JS, Hierro A 2016. Structural mechanism for cargo recognition by the retromer complex. Cell 167:1623–35
    [Google Scholar]
  104. 104.  Luck AN, Mason AB 2012. Transferrin-mediated cellular iron delivery. Curr. Top. Membr. 69:3–35
    [Google Scholar]
  105. 105.  Luck AN, Mason AB 2013. Structure and dynamics of drug carriers and their interaction with cellular receptors: focus on serum transferrin. Adv. Drug Deliv. Rev. 65:1012–19
    [Google Scholar]
  106. 106.  Mancias JD, Wang X, Gygi SP, Harper JW, Kimmelman AC 2014. Quantitative proteomics identifies NCOA4 as the cargo receptor mediating ferritinophagy. Nature 509:105–9
    [Google Scholar]
  107. 107.  Martin DN, Uprichard SL 2013. Identification of transferrin receptor 1 as a hepatitis C virus entry factor. PNAS 110:10777–82
    [Google Scholar]
  108. 108.  Martys JL, Wjasow C, Gangi DM, Kielian MC, McGraw TE, Backer JM 1996. Wortmannin-sensitive trafficking pathways in Chinese hamster ovary cells: differential effects on endocytosis and lysosomal sorting. J. Biol. Chem. 271:10953–62
    [Google Scholar]
  109. 109.  Mason AL, Gilady SY, Mackey JR 2011. Mouse mammary tumor virus in human breast cancer: red herring or smoking gun?. Am. J. Pathol. 179:1588–90
    [Google Scholar]
  110. 110.  Maxfield FR, McGraw TE 2004. Endocytic recycling. Nat. Rev. Mol. Cell Biol. 5:121–32
    [Google Scholar]
  111. 111.  Maxson ME, Grinstein S 2014. The vacuolar-type H+-ATPase at a glance—more than a proton pump. J. Cell Sci. 127:4987–93
    [Google Scholar]
  112. 112.  Mayle KM, Le AM, Kamei DT 2012. The intracellular trafficking pathway of transferrin. Biochim. Biophys. Acta 1820:264–81
    [Google Scholar]
  113. 113.  McClelland A, Kuhn LC, Ruddle FH 1984. The human transferrin receptor gene: genomic organization, and the complete primary structure of the receptor deduced from a cDNA sequence. Cell 39:267–74
    [Google Scholar]
  114. 114.  McGraw TE, Greenfield L, Maxfield FR 1987. Functional expression of the human transferrin receptor cDNA in Chinese hamster ovary cells deficient in endogenous transferrin receptor. J. Cell Biol. 105:207–14
    [Google Scholar]
  115. 115.  Motley A, Bright NA, Seaman MN, Robinson MS 2003. Clathrin-mediated endocytosis in AP-2-depleted cells. J. Cell Biol. 162:909–18
    [Google Scholar]
  116. 116.  Moura IC, Arcos-Fajardo M, Sadaka C, Leroy V, Benhamou M et al. 2004. Glycosylation and size of IgA1 are essential for interaction with mesangial transferrin receptor in IgA nephropathy. J. Am. Soc. Nephrol. 15:622–34
    [Google Scholar]
  117. 117.  Moura IC, Centelles MN, Arcos-Fajardo M, Malheiros DM, Collawn JF et al. 2001. Identification of the transferrin receptor as a novel immunoglobulin (Ig)A1 receptor and its enhanced expression on mesangial cells in IgA nephropathy. J. Exp. Med. 194:417–25
    [Google Scholar]
  118. 118.  Muckenthaler MU, Rivella S, Hentze MW, Galy B 2017. A red carpet for iron metabolism. Cell 168:344–61
    [Google Scholar]
  119. 119.  Nai A, Lidonnici MR, Rausa M, Mandelli G, Pagani A et al. 2015. The second transferrin receptor regulates red blood cell production in mice. Blood 125:1170–79
    [Google Scholar]
  120. 120.  Ned RM, Swat W, Andrews NC 2003. Transferrin receptor 1 is differentially required in lymphocyte development. Blood 102:3711–18
    [Google Scholar]
  121. 121.  Nekhai S, Kumari N, Dhawan S 2013. Role of cellular iron and oxygen in the regulation of HIV-1 infection. Future Virol 8:301–11
    [Google Scholar]
  122. 122.  Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A et al. 2004. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306:2090–93
    [Google Scholar]
  123. 123.  Nunberg JH, York J 2012. The curious case of arenavirus entry, and its inhibition. Viruses 4:83–101
    [Google Scholar]
  124. 124.  Oppenheimer SJ 2001. Iron and its relation to immunity and infectious disease. J. Nutr. 131:616S–33S
    [Google Scholar]
  125. 125.  Palermo LM, Hueffer K, Parrish CR 2003. Residues in the apical domain of the feline and canine transferrin receptors control host-specific binding and cell infection of canine and feline parvoviruses. J. Virol. 77:8915–23
    [Google Scholar]
  126. 126.  Park GS, Best SM, Bloom ME 2005. Two mink parvoviruses use different cellular receptors for entry into CRFK cells. Virology 340:1–9
    [Google Scholar]
  127. 127.  Parker JS, Murphy WJ, Wang D, O'Brien SJ, Parrish CR 2001. Canine and feline parvoviruses can use human or feline transferrin receptors to bind, enter, and infect cells. J. Virol. 75:3896–902
    [Google Scholar]
  128. 128.  Peng YY, Uprichard J 2017. Ferritin and iron studies in anaemia and chronic disease. Ann. Clin. Biochem. 54:43–48
    [Google Scholar]
  129. 129.  Philpott CC, Ryu MS 2014. Special delivery: distributing iron in the cytosol of mammalian cells. Front. Pharmacol. 5:173
    [Google Scholar]
  130. 130.  Radoshitzky SR, Abraham J, Spiropoulou CF, Kuhn JH, Nguyen D et al. 2007. Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses. Nature 446:92–96
    [Google Scholar]
  131. 131.  Radoshitzky SR, Kuhn JH, Spiropoulou CF, Albarino CG, Nguyen DP et al. 2008. Receptor determinants of zoonotic transmission of New World hemorrhagic fever arenaviruses. PNAS 105:2664–69
    [Google Scholar]
  132. 132.  Recalcati S, Gammella E, Buratti P, Cairo G 2017. Molecular regulation of cellular iron balance. IUBMB Life 69:389–98
    [Google Scholar]
  133. 133.  Robb AD, Ericsson M, Wessling-Resnick M 2004. Transferrin receptor 2 mediates a biphasic pattern of transferrin uptake associated with ligand delivery to multivesicular bodies. Am. J. Physiol. Cell Physiol. 287:C1769–75
    [Google Scholar]
  134. 134.  Robb AD, Wessling-Resnick M 2004. Regulation of transferrin receptor 2 protein levels by transferrin. Blood 104:4294–99
    [Google Scholar]
  135. 135.  Rose PP, Hanna SL, Spiridigliozzi A, Wannissorn N, Beiting DP et al. 2011. Natural resistance–associated macrophage protein is a cellular receptor for Sindbis virus in both insect and mammalian hosts. Cell Host Microbe 10:97–104
    [Google Scholar]
  136. 136.  Ross SR, Schofield JJ, Farr CJ, Bucan M 2002. Mouse transferrin receptor 1 is the cell entry receptor for mouse mammary tumor virus. PNAS 99:12386–90
    [Google Scholar]
  137. 137.  Rutledge EA, Enns CA 1996. Cleavage of the transferrin receptor is influenced by the composition of the O-linked carbohydrate at position 104. J. Cell. Physiol. 168:284–93
    [Google Scholar]
  138. 138.  Ryu MS, Zhang D, Protchenko O, Shakoury-Elizeh M, Philpott CC 2017. PCBP1 and NCOA4 regulate erythroid iron storage and heme biosynthesis. J. Clin. Investig. 127:1786–97
    [Google Scholar]
  139. 139.  Salmeron A, Borroto A, Fresno M, Crumpton MJ, Ley SC, Alarcon B 1995. Transferrin receptor induces tyrosine phosphorylation in T cells and is physically associated with the TCR zeta-chain. J. Immunol. 154:1675–83
    [Google Scholar]
  140. 140.  Sarute N, Ross SR 2017. New World arenavirus biology. Annu. Rev. Virol. 4:141–58
    [Google Scholar]
  141. 141.  Senyilmaz D, Virtue S, Xu X, Tan CY, Griffin JL et al. 2015. Regulation of mitochondrial morphology and function by stearoylation of TFR1. Nature 525:124–28
    [Google Scholar]
  142. 142.  Sheftel AD, Mason AB, Ponka P 2012. The long history of iron in the Universe and in health and disease. Biochim. Biophys. Acta 1820:161–87
    [Google Scholar]
  143. 143.  Sheftel AD, Zhang AS, Brown C, Shirihai OS, Ponka P 2007. Direct interorganellar transfer of iron from endosome to mitochondrion. Blood 110:125–32
    [Google Scholar]
  144. 144.  Shi H, Bencze KZ, Stemmler TL, Philpott CC 2008. A cytosolic iron chaperone that delivers iron to ferritin. Science 320:1207–10
    [Google Scholar]
  145. 145.  Shu ST, Emert-Sedlak LA, Smithgall TE 2017. Cell-based fluorescence complementation reveals a role for HIV-1 Nef protein dimerization in AP-2 adaptor recruitment and CD4 co-receptor down-regulation. J. Biol. Chem. 292:2670–78
    [Google Scholar]
  146. 146.  Spiro DJ, Boll W, Kirchhausen T, Wessling-Resnick M 1996. Wortmannin alters the transferrin receptor endocytic pathway in vivo and in vitro. Mol. Biol. Cell 7:355–67
    [Google Scholar]
  147. 147.  Steere AN, Chasteen ND, Miller BF, Smith VC, MacGillivray RT, Mason AB 2012. Structure-based mutagenesis reveals critical residues in the transferrin receptor participating in the mechanism of pH-induced release of iron from human serum transferrin. Biochemistry 51:2113–21
    [Google Scholar]
  148. 148.  Stiles KM, Kielian M 2011. Alphavirus entry: NRAMP leads the way. Cell Host Microbe 10:92–93
    [Google Scholar]
  149. 149.  Sun JZ, Wang J, Wang S, Yuan D, Li Z et al. 2014. MicroRNA miR-320a and miR-140 inhibit mink enteritis virus infection by repression of its receptor, feline transferrin receptor. Virol. J. 11:210
    [Google Scholar]
  150. 150.  Tachiyama R, Ishikawa D, Matsumoto M, Nakayama KI, Yoshimori T et al. 2011. Proteome of ubiquitin/MVB pathway: possible involvement of iron-induced ubiquitylation of transferrin receptor in lysosomal degradation. Genes Cells 16:448–66
    [Google Scholar]
  151. 151.  TerBush DR, Maurice T, Roth D, Novick P 1996. The exocyst is a multiprotein complex required for exocytosis in Saccharomyces cerevisiae. . EMBO J 15:6483–94
    [Google Scholar]
  152. 152.  Touret N, Furuya W, Forbes J, Gros P, Grinstein S 2003. Dynamic traffic through the recycling compartment couples the metal transporter Nramp2 (DMT1) with the transferrin receptor. J. Biol. Chem. 278:25548–57
    [Google Scholar]
  153. 153.  Traer CJ, Rutherford AC, Palmer KJ, Wassmer T, Oakley J et al. 2007. SNX4 coordinates endosomal sorting of TfnR with dynein-mediated transport into the endocytic recycling compartment. Nat. Cell Biol. 9:1370–80
    [Google Scholar]
  154. 154.  Trenor CC3rd, Campagna DR, Sellers VM, Andrews NC, Fleming MD 2000. The molecular defect in hypotransferrinemic mice. Blood 96:1113–18
    [Google Scholar]
  155. 155.  Vogt TM, Blackwell AD, Giannetti AM, Bjorkman PJ, Enns CA 2003. Heterotypic interactions between transferrin receptor and transferrin receptor 2. Blood 101:2008–14
    [Google Scholar]
  156. 156.  Wallace DF, Summerville L, Subramaniam VN 2007. Targeted disruption of the hepatic transferrin receptor 2 gene in mice leads to iron overload. Gastroenterology 132:301–10
    [Google Scholar]
  157. 157.  Wandinger-Ness A, Zerial M 2014. Rab proteins and the compartmentalization of the endosomal system. Cold Spring Harb. Perspect. Biol. 6:a022616
    [Google Scholar]
  158. 158.  Wang E, Albritton L, Ross SR 2006. Identification of the segments of the mouse transferrin receptor 1 required for mouse mammary tumor virus infection. J. Biol. Chem. 281:10243–49
    [Google Scholar]
  159. 159.  Wang E, Obeng-Adjei N, Ying Q, Meertens L, Dragic T et al. 2008. Mouse mammary tumor virus uses mouse but not human transferrin receptor 1 to reach a low pH compartment and infect cells. Virology 381:230–40
    [Google Scholar]
  160. 160.  Watts C 1985. Rapid endocytosis of the transferrin receptor in the absence of bound transferrin. J. Cell Biol. 100:633–37
    [Google Scholar]
  161. 161.  Weinberg ED 1996. Iron withholding: a defense against viral infections. BioMetals 9:393–99
    [Google Scholar]
  162. 162.  Weiss G, Carver PL 2017. Role of divalent metals in infectious disease susceptibility and outcome. Clin. Microbiol. Infect. 24:16–23
    [Google Scholar]
  163. 163.  Wen J, Pan S, Liang S, Zhong Z, He Y et al. 2013. Soluble form of canine transferrin receptor inhibits canine parvovirus infection in vitro and in vivo. BioMed Res. Int. 2013:172479
    [Google Scholar]
  164. 164.  Wessling-Resnick M 2010. Iron homeostasis and the inflammatory response. Annu. Rev. Nutr. 30:105–22
    [Google Scholar]
  165. 165.  Wessling-Resnick M 2015. Nramp1 and other transporters involved in metal withholding during infection. J. Biol. Chem. 290:18984–90
    [Google Scholar]
  166. 166.  West AP Jr., Bennett MJ, Sellers VM, Andrews NC, Enns CA, Bjorkman PJ 2000. Comparison of the interactions of transferrin receptor and transferrin receptor 2 with transferrin and the hereditary hemochromatosis protein HFE. J. Biol. Chem. 275:38135–38
    [Google Scholar]
  167. 167.  White RA, Boydston LA, Brookshier TR, McNulty SG, Nsumu NN et al. 2005. Iron metabolism mutant hbd mice have a deletion in Sec15l1, which has homology to a yeast gene for vesicle docking. Genomics 86:668–73
    [Google Scholar]
  168. 168.  Worthen CA, Enns CA 2014. The role of hepatic transferrin receptor 2 in the regulation of iron homeostasis in the body. Front. Pharmacol. 5:34
    [Google Scholar]
  169. 169.  Xia H, Anderson B, Mao Q, Davidson BL 2000. Recombinant human adenovirus: Targeting to the human transferrin receptor improves gene transfer to brain microcapillary endothelium. J. Virol. 74:11359–66
    [Google Scholar]
  170. 170.  Xu W, Barrientos T, Mao L, Rockman HA, Sauve AA, Andrews NC 2015. Lethal cardiomyopathy in mice lacking transferrin receptor in the heart. Cell Rep 13:533–45
    [Google Scholar]
  171. 171.  Yanatori I, Yasui Y, Tabuchi M, Kishi F 2014. Chaperone protein involved in transmembrane transport of iron. Biochem. J. 462:25–37
    [Google Scholar]
  172. 172.  Yang B, Hoe MH, Black P, Hunt RC 1993. Role of oligosaccharides in the processing and function of human transferrin receptors: effect of the loss of the three N-glycosyl oligosaccharides individually or together. J. Biol. Chem. 268:7435–41
    [Google Scholar]
  173. 173.  Yang FM, Friedrichs WE, Buchanan JM, Herbert DC, Weaker FJ et al. 1990. Tissue specific expression of mouse transferrin during development and aging. Mech. Ageing Dev. 56:187–97
    [Google Scholar]
  174. 174.  Zapata JC, Salvato MS 2013. Arenavirus variations due to host-specific adaptation. Viruses 5:241–78
    [Google Scholar]
  175. 175.  Zeltina A, Krumm SA, Sahin M, Struwe WB, Harlos K et al. 2017. Convergent immunological solutions to Argentine hemorrhagic fever virus neutralization. PNAS 114:7031–36
    [Google Scholar]
  176. 176.  Zhang AS, Sheftel AD, Ponka P 2005. Intracellular kinetics of iron in reticulocytes: evidence for endosome involvement in iron targeting to mitochondria. Blood 105:368–75
    [Google Scholar]
  177. 177.  Zhang AS, Xiong S, Tsukamoto H, Enns CA 2004. Localization of iron metabolism–related mRNAs in rat liver indicate that HFE is expressed predominantly in hepatocytes. Blood 103:1509–14
    [Google Scholar]
  178. 178.  Zhao N, Enns CA 2013. N-linked glycosylation is required for transferrin-induced stabilization of transferrin receptor 2, but not for transferrin binding or trafficking to the cell surface. Biochemistry 52:3310–19
    [Google Scholar]
  179. 179.  Zong M, Fofana I, Choe H 2014. Human and host species transferrin receptor 1 use by North American arenaviruses. J. Virol. 88:9418–28
    [Google Scholar]
  180. 180.  Zumerle S, Mathieu JR, Delga S, Heinis M, Viatte L et al. 2014. Targeted disruption of hepcidin in the liver recapitulates the hemochromatotic phenotype. Blood 123:3646–50
    [Google Scholar]
/content/journals/10.1146/annurev-nutr-082117-051749
Loading
/content/journals/10.1146/annurev-nutr-082117-051749
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error