TfR2 localizes in lipid raft domains and is released in exosomes to activate signal transduction along the MAPK pathway

Journal of Cell Science

Volumn 119, Issue 21, 2006, Pages 4486-4498

  Calzolari, Alessia ^a   Raggi, Carla ^a   Deaglio, Silvia ^b   Sposi, Nadia Maria ^a   Stafsnes, Marit ^a   Fecchi, Katia ^a   Parolini, Isabella ^a   Malavasi, Fabio ^b   Peschle, Cesare ^a   Sargiacomo, Massimo ^a   Testa, Ugo ^a  

^a ISTITUTO SUPERIORE DI SANITÀ   (Italy)

^b UNIVERSITY OF TURIN   (Italy)

Author keywords

Cell signalling; Iron metabolism; Lipid rafts; Transferrin

Indexed keywords

CAVEOLIN 1; CD71 ANTIGEN; CD81 ANTIGEN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE P38; RECEPTOR ANTIBODY; TETRASPANIN; TRANSFERRIN RECEPTOR 2;

ARTICLE; CELL FRACTIONATION; CELL MEMBRANE; CELL ORGANELLE; CELL STRAIN HEPG2; CELL STRAIN K 562; CONTROLLED STUDY; CULTURE MEDIUM; ENDOCYTOSIS; ENDOSOME; ENZYME ACTIVATION; FLOW CYTOMETRY; HUMAN; HUMAN CELL; IMMUNOPRECIPITATION; INTERNALIZATION; LIPID RAFT; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN LOCALIZATION; SIGNAL TRANSDUCTION; WESTERN BLOTTING;

ANTIGENS, CD; BLOTTING, WESTERN; CARCINOMA, HEPATOCELLULAR; CAVEOLIN 1; CELL MEMBRANE; CELLS, CULTURED; ENDOCYTOSIS; FLOW CYTOMETRY; HUMANS; IMMUNOPRECIPITATION; K562 CELLS; LIVER NEOPLASMS; MEMBRANE MICRODOMAINS; MITOGEN-ACTIVATED PROTEIN KINASES; PHOSPHORYLATION; RECEPTORS, TRANSFERRIN; SIGNAL TRANSDUCTION; SUBCELLULAR FRACTIONS; TRANSPORT VESICLES;

BOS TAURUS;

EID: 33751549663     PISSN: 00219533     EISSN: None     Source Type: Journal    
DOI: 10.1242/jcs.03228     Document Type: Article

References (70)

1. Bard, M. P., Hegmans, J. P., Hemmes, A., Luider, T. M., Willemsen, R., Severijnen, L. A., Van Meerbeeck, J. P.., Burgers, S. A., Hoogsteden, H. C. and Lambrecht, B. N. (2004). Proteomic analysis of exosomes isolated from human malignant pleural effusions. Am. J. Respir Cell Mol. Biol. 31, 114-121.
2. Blanchard, N., Lankar, D., Faure, F., Regnault, A., Dumont, C., Raposo, G. and Hivroz, C. (2002). TCR activation of human T cells induce the production of exosomes bearing the TCR/CD3/zeta complex. J. Immunol. 168, 3235-3241.
3. Caby, M. P., Lankar, D., Vincendeau-Scherrer, C., Raposo, G. and Bonerrot, C. (2005). Exosomal-like vesicles are present in human blood plasma. Int. Immunol. 17, 879-887.
4. Camaschella, C., Roetto, A., Cali, A., De Gobbi, M., Garozzo, G., Carella., M., Majorano, N., Totaro, A. and Gasparini, R (2000). The gene TFR2 is mutated in a new type of hemochromatosis mapping to 7q22. Nat. Genet. 25, 14-15.
5. Couzin, J. (2005). The ins and outs of exosomes. Science 308, 1862-1863.
6. De Gassart, A., Géminard, C., Février, B., Raposo, G. and Vidal, M. (2003). Lipid raft-associated protein sorting in exosomes. Blood 102, 4336-4344.
7. Deaglio, S., Capobianco, A., Cali, A., Bellora, F., Alberti, R, Righil, L., Sapìno, A., Camaschella, C. and Malavasi, F. (2002). Structural, functional, and tissue distribution analysis of human transferrin receptor-2 by murine monoclonal antibodies and a polyclonal antiserum. Blood 100, 3782-3789.
8. Demeule, M., Bertrand, Y., Michaud-Levesque, J., Jodoin, J., Rolland, Y., Gabathuler, R. and Béliveau, R. (2003). Regulation of plasminogen activation: a role for melanotransferrin (p97) in cell migration. Blood 102, 1723-1731.
9. Denzer, K., Kleijmeer, M. J., Heijnen, H. F. G., Stoorvogel, W. and Geuze, H. J. (2000). Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J. Cell Sci. 113, 3365-3374.
10. Escola, J. M., Kleijmeer, M. J., Stoorvogel, W., Griffith, J. M., Yoshie, O. and Geuze, H. J. (1998). Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes. J. Biol. Chem. 273, 20121-20127.
11. Février, B., Vilette, D., Archer, F., Loew, W., Faigle, W., Vidal, M., Laude, H. and Raposo, G. (2004). Cells release prions in association with exosomes. Proc. Natl. Acad. Sci. USA 101, 9683-9688.
12. Fleming, R. E., Migas, M. C., Holden, C. C., Waheed, A., Britton, R. S., Tomatsu, S., Bacon, B. R. and Sly, W. S. (2000). Transferrin receptor 2, continued expression in mouse liver in the face of iron overload and in hereditary hemochromatosis. Proc. Natl. Acad. Sci. USA 97, 2214-2219.
13. Food, M. R., Rothenberger, S., Gabathuler, R., Haidl, I. D., Reid, G. and Jefferies, W. A. (1994). Transport and expression in human melanomas of a transferrin-like glycophosphatidylinositol-anchored protein. J. Biol. Chem. 269, 3034-3040.
14. Gehrke, S. G., Kulaksiz, H., Hermann, T., Riedel, H. D., Bents, K., Veltkamp, C. and Stremmel, W. (2003). Expression of hepcidin in hereditary hemochromatosis: evidence for a regulation in response to serum transferrin saturation and non-transferrin-bound iron. Blood 102, 371-376.
15. Géminard, C., De Gassart, A., Blanc, L. and Vidal, M. (2004). Degradation of AP2 during reticulocyte maturation enhances binding of Hsc70 and Alix to a common site on TfR for sorting into exosomes. Traffic 5, 181-193.
16. Glockner, G., Scherer, S., Schattevoy, R., Boright, A., Weber, J., Tsui, L. C., Boright, A., Weber, J., Tsui, L. C. and Rosenthal, A. (1998). Large-scale sequencing of two regions in human chromosome 7q22: analysis of 650 Kb of genomic sequence around the EPO and CUTL1 loci reveals 17 genes. Genome Res. 8, 1060-1073.
17. Gombos, I., Bacsó, Z., Detre, C., Nagy, H., Goda, K., Andrásfalvy, M., Szabó, G. and Matkó, J. (2004). Cholesterol sensitivity of detergent resistance: a rapid flow cytometric test for detecting constitutive or induced raft association of membrane proteins. Cytometry A 61, 117-126.
18. Griffiths, W. J. H. and Cox, T. M. (2003). Co-localization of the mammalian hemochromatosis gene product (HFE) and a newly identified transferrin receptor (TfR2) in intestinal tissue and cells. J. Histochem. 51, 613-623.
19. Gutwein, P., Stoeck, A., Riedle, S., Gast, D., Runz, S., Condon, T. P., Marmé, A., Phong, M. C., Linderkamp, O., Skorokhod, A. et al. (2005). Cleavage of L1 in exosomes and apoptotic membrane vesicles released from ovarian carcinoma cells. Clin. Cancer Res. 11, 2492-2501.
20. Hegmans, J. P., Bard, M. P., Hemmes, A., Luider, T. M., Kleijmeer, M. J., Prins, J. B., Zitvogel, L., Burgers, S. A., Hoogsteden, H. C. and Lambrecht, B. N. (2004). Proteomic analysis of exosomes secreted by human mesothelioma cells. Am. J. Pathol. 164, 1807-1815.
21. Hemler, M. E. (2003). Tetraspanin proteins mediate cellular penetration, invasion, and fusion events and define a novel type of membrane microdomain. Annu. Rev. Cell Dev. Biol. 19, 397-422.
22. Johnson, M. B. and Enns, C. A. (2004). Diferric transferrin regulates transferrin receptor 2 protein stability. Blood 104, 4287-4293.
23. Johnstone, R. M. (2005). Revisiting the road to the discovery of exosomes. Blood Cells Mol. Dis. 34, 214-219.
24. Kawabata, H., Yang, R., Hirama, T., Wong, P. T., Kawano, S., Gombart, A. F. and Koeffler, H. P. (1999). Molecular cloning of transferrin receptor 2. A new member of the transferrin receptor-like family. J. Biol. Chem. 274, 20826-20832.
25. Kawabata, H., Germain, R. S., Vuong, P. T., Nakamaki, T., Said, J. W. and Koeffler, H. P. (2000). Transferrin receptor 2-alpha supports cell growth both in iron-chelated cultured cells and in vivo. J. Biol. Chem. 275, 16618-16625.
26. Kawabata, H., Germain, R. S., Ikezoe, T., Tong, X., Green, E. M., Gombart, A. F. and Koeffler, H. P. (2001). Regulation of expression of murine transferrin receptor 2. Blood 98, 1949-1954.
27. Kawabata, H., Tong, X., Kawanami, T., Wano, Y., Hirose, Y., Sugai, S. and Koeffler, H. P. (2004). Analyses for binding of the transferrin family of proteins to the transferrin receptor 2. Br. J. Haematol. 127, 464-473.
28. Kawabata, H., Fleming, R. E., Gui, D., Moon, S. Y., Takayuki, S., O'Kelly, J., Umehara, Y., Wano, Y., Said, J. W. and Koeffler, H. P. (2005). Expression of hepcidin is down-regulated in TfR2 mutant mice manifesting a phenotype of hereditary hemochromatosis. Blood 105, 376-381.
29. Kennard, M. L., Richardson, D. R., Gabathuler, R., Ponka, P. and Jefferies, W. A. (1995). A novel iron uptake mechanism mediated by GPI-anchored human p97. EMBO J. 14, 4178-4186.
30. Krajewska, W. M. and Maslowska, I. (2004). Caveolins: structure and function in signal transduction. Cell. Mol. Biol. Lett. 9, 195-220.
31. Lagasse, E., Connors, H., Al-Dhalimy, M., Reitsma, M., Dohse, M., Osborne, L., Wang, X., Finegold, M., Weissman, I. L. and Grompe, M. (2000). Purified hematopoietic stem cells can differenziate into hepatocytes in vivo. Nat. Med. 6, 1229-1234.
32. Lamb, J. E., Ray, F., Ward, J. H., Kusher, J. P. and Kaplan, J. (1983). Internalization and subcellular localization of transferrin and transferrin receptors in HeLa cells. J. Biol. Chem. 258, 8751-8758.
33. Levy, S. and Shoham, T. (2005). The tetraspanin web modulates immune-signalling complexes. Nat. Rev. Immunol. 5, 136-148.
34. Li, Y. C., Park, M. J., Ye, S. K., Kim, C. W. and Kim, Y. N. (2006). Elevated levels of cholesterol-rich lipid rafts in cancer cells are correlated with apoptosis sensitivity induced by cholesterol-depleting agents. Am. J. Pathol. 168, 1107-1118.
35. Lisanti, M. P., Tang, Z. L. and Sargiacomo, M. (1993). Caveolin forms a hetero-oligomeric protein complex that interacts with an apical GPI-linked protein: implications for the biogenesis of caveolae. J. Cell Biol. 123, 595-604.
36. Masciopinto, F., Giovani, C., Campagnoli, S., Galli-Stampino, L., Colombatto, P., Brunetto, M., Yen, B. T. S., Houghton, M., Pileri, P. and Abrignani, S. (2004). Association of hepatitis C virus envelope proteins with exosomes. Eur. J. Immunol. 34, 2834-2842.
37. Matthews, L. C., Taggart, M. J. and Westwood, M. (2005). Effect of cholesterol depletion on mitogenesis and survival: the role of caveolar and noncaveolar domains in insuline-like growth factor-mediated cellular function. Endocrinology 146, 5463-5473.
38. Mazzocca, A., Cappadona Sciammetta, S., Carloni, V., Cosmi, L., Annunziato, F., Harada, T., Abrignani, S. and Pinzani, M. (2005). Binding of Hepatitis C Virus envelope protein E2 to CD81 up-regulates matrix metalloproteinase-2 in human hepatic stellate cells. J. Biol. Chem. 280, 11329-11339.
39. Mifuji, R., Kobayashi, Y., Ma, N., Quing, Q. L., Urawa, N., Horiike, S., Iwasa, M., Kaito, M., Malavasi, F. and Adachi, Y. (2006). Role of transferrin receptor 2 in hepatic accumulation of iron in patients with chronic hepatitis C. J. Gastroenterol. Hepatol. 21, S144-S151.
40. Nemeth, E., Roetto, A., Garozzo, G., Ganz, T. and Camaschella, C. (2005). Hepcidin is decreased in TfR2 hemochromatosis. Blood 105, 1803-1806.
41. Nguyen, D. G., Booth, A., Gould, S. J. and Hildreth, J. E. (2003). Evidence that HIV budding in primary macrophages occurs through the exosome release pathway. J. Biol. Chem. 278, 52347-52354.
42. Nowak, G., Ericzon, B. G., Nava, S., Jaksach, M., Westgren, M. and Sumitran-Holgersson, S. (2005). Identification of expandable human hepatic progenitors which differentiate into mature hepatic cells in vivo. Gut 54, 972-979.
43. Park, C. H., Valore, E. V., Waring, A. J. and Ganz, T. (2001). Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J. Biol. Chem. 276, 7806-7810.
44. Parolini, I., Sargiacomo, M., Lisainti, M. P. and Peschle, C. (1996). Signal transduction and glycophosphatidylinositol-linked proteins (lyn, Ick, CD4, CD45, G proteins, and CD55) selectively localize in Triton-insoluble plasma membrane domains of human leukemic cell lines and normal granulocytes. Blood 87, 3783-3794.
45. Parolini, I., Sargiacomo, M., Galbiati, F., Rizzo, G., Grignani, F., Engelman, J. A., Okamoto, T., Ikezu, T., Sherer, P. E., Mora, R. et al. (1999). Expression of caveolin-1 is required for the transport of caveolin-2 to the plasma membrane. Retention of caveolin-2 at the level of the Golgi complex. J. Biol. Chem. 274, 25718-25725.
46. Parton, R. G. (2003). Caveolae - from ultrastructure to molecular mechanism. Nat. Rev. Mol. Cell Biol. 4, 162-167.
47. Pelchen-Matthews, A., Raposo, G. and Marsh, M. (2004). Endosomes, exosomes and Trojan viruses. Trends Microbiol. 12, 310-316.
48. Pelkmans, L., Burli, T., Zerial, M. and Helenius, A. (2004). Caveolin-stabilized membrane domains as multifunctional transport and sorting devices in endocytic membrane traffic. Cell 118, 767-780.
49. Pigeon, C. Ilyn, G., Courselaud, B., Leroyer, F., Turlin, B., Brissot, P. and Loreal, O. (2001). A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J. Biol. Chem. 276, 7811-7819.
50. Rabesandratana, H., Toutant, J. P., Reggio, H. and Vidal, M. (1998). Decay-accelerating factor (CD55) and the membrane inhibitor of reactive lysis (CD59) are released within exosomes during in vitro maturation of reficulocytes. Blood 91, 2573-2580.
51. Riteau, B., Faure, F., Menier, C., Viel, S., Carosella, E. D., Amigorena, S. and Rouas-Freiss, N. (2003). Exosomes bearing HLA-G are secreted by melanoma cells. Hum. Inummol. 64, 1064-1072.
52. Robb, A. D., Ericsson, M. and 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, C1768-C1775.
53. Roetto, A., Daraio, F., Alberti, F., Porporato, P., Cali, A., De Gobbi, M. and Camaschella, C. (2002). Hemochromatosis due to mutations in transferrin receptor 2. Blood Cells Mol. Dis. 29, 465-470.
54. Sala, R., Jefferies, W. A., Walker, B., Yang, J., Tiong, J., Law, S. K., Carlevaro, M. F., Di Marco, E., Vacca, A., Cancedda, R. et al. (2002). The human melanoma associated protein metanotransferrin promotes endothelial cell migration and angiogenesis in vivo. Eur. J. Cell Biol. 81, 599-607.
55. Sargiacomo, M., Lisanti, M. P., Graeve, L., Le Bivic, A. and Rodriguez-Boulan, E. (1989). Integral and peripheral protein composition of the apical and basolateral membrane domains in MDCK cells. J. Membr. Biol. 107, 277-286.
56. Savina, A., Vidal, M. and Colombo, M. I. (2002). The exosome pathway in K562 cells is regulated by Rab11. J. Cell Sci. 115, 2505-2515.
57. Savina, A., Furlàn, M., Vidal, M. and Colombo, M. I. (2003). Exosome release is regulated by a calcium-dependent mechanism in K562 cells. J. Biol. Chem. 278, 20083-20090.
58. Sebolt-Leopold, J. S. and Herrera, R. (2004). Targeting the mitogen-activated protein kinase cascade to treat cancer. Nat. Rev. Cancer 4, 937-947.
59. Simons, K. and Toomre, D. (2000). Lipid rafts and signal transduction. Nat. Rev. Mol. Cell Biol. 1, 31-39.
60. Sönnichsen, B., De Renzis, S., Nielsen, E., Rietdorf, J. and Zerial, M. (2000). Distinct membrane domains on endosomes in the recycling pathway visualized by multicolour imaging of Rab4, Rab5, and Rab11. J. Cell Biol. 149, 901-913.
61. Takeo, M., Kobayashi, Y., Fujita, N., Urawa, N., Iwasa, M., Horiike, S., Tanaka, H., Kaito, M. and Adachi, Y. (2005). Upregulation of transferrin receptor 2 and fierroportin 1 mRNA in the liver of patients with chronic hepatitis C. Hepatology 20, 562-569.
62. Théry, C., Boussac, M., Véron, P., Ricciardi-Castagnoli, P., Raposo, G., Garin, J. and Amigorena, S. (2001). Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J. Immunol. 166, 7309-7318.
63. Théry, C., Zitvogel, L. and Amigorena, S. (2002). Exosomes: composition, biogenesis and function. Nat. Rev. Immunol. 2, 569-579.
64. Trischler, M., Stoorvogel, W. and Ullrich, O. (1999). Biochemical analysis of distinct Rab5- and Rab11-positive endosomes along the transferrin pathway. J. Cell Sci. 112, 4773-4783.
65. Van Niel, G., Raposo, G., Candalh, C., Boussac, M., Hershberg, R., Cerf-Bensussan, N. and Heyman, M. (2001). Intestinal epithelial cells secrete exosome-like vesicles. Gastroenterology 121, 337-349.
66. Vidal, M. J. and Stahl, P. D. (1993). The small GTP-binding proteins Rab4 and ARF are associated with vesicles released during reticulocyte maturation. Eur. J. Cell Biol. 60, 261-267.
67. Wallace, D. F., Summerville, L., Lusby, P. E. and Subramaniam, V. N. (2005). First phenotypic description of transferrin receptor 2 knockout mouse, and the role of hepcidin. Gut 54, 980-986.
68. Watts, C. (1985). Rapid endocytosis of the transferrin receptor in the absence of bound transferrin. J. Cell Biol. 100, 633-637.
69. Wolfers, J., Lozier, A., Raposo, G., Regnault, A., Théry, C., Masurier, C., Flement, C., Pouzieux, S., Faure, S., Tursz, T. et al. (2001). Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat. Med. 7, 297-303.
70. Yang, N., Huang, Y., Jiang, J. and Frank, S. J. (2004). Caveolar and lipid raft localization of the growth hormone receptor and its signalling. J. Biol. Chem. 279, 20898-20905.