Advertisement
Journal Article
Exosome: from internal vesicle of the multivesicular body to intercellular signaling device
K. Denzer, M.J. Kleijmeer, H.F. Heijnen, W. Stoorvogel, H.J. Geuze
Journal of Cell Science 2000 113: 3365-3374;

Summary

Exosomes are small membrane vesicles that are secreted by a multitude of cell types as a consequence of fusion of multivesicular late endosomes/lysosomes with the plasma membrane. Depending on their origin, exosomes can play roles in different physiological processes. Maturing reticulocytes externalize obsolete membrane proteins such as the transferrin receptor by means of exosomes, whereas activated platelets release exosomes whose function is not yet known. Exosomes are also secreted by cytotoxic T cells, and these might ensure specific and efficient targeting of cytolytic substances to target cells. Antigen presenting cells, such as B lymphocytes and dendritic cells, secrete MHC class-I- and class-II-carrying exosomes that stimulate T cell proliferation in vitro. In addition, dendritic-cell-derived exosomes, when used as a cell-free vaccine, can eradicate established murine tumors. Although the precise physiological target(s) and functions of exosomes remain largely to be resolved, follicular dendritic cells (accessory cells in the germinal centers of secondary lymphoid organs) have recently been shown to bind B-lymphocyte-derived exosomes at their cell surface, which supports the notion that exosomes play an immunoregulatory role. Finally, since exosomes are derived from multivesicular bodies, their molecular composition might provide clues to the mechanism of protein and lipid sorting in endosomes.

REFERENCES

    1. Advani, R. J.,
    2. Yang, B.,
    3. Prekeris, R.,
    4. Lee, K. C.,
    5. Klumperman, J. and
    6. Scheller, R. H.
    (1999). VAMP-7 mediates vesicular transport from endosomes to lysosomes. J. Cell Biol 146, 765–776
    OpenUrlAbstract/FREE Full Text
    1. Albert, M. L.,
    2. Sauter, B. and
    3. Bhardwaj, N.
    (1998). Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature 392, 86–89
    OpenUrlCrossRefPubMedWeb of Science
    1. Amigorena, S.,
    2. Webster, P.,
    3. Drake, J.,
    4. Newcomb, J.,
    5. Cresswell, P. and
    6. Mellman, I.
    (1995). Invariant chain cleavage and peptide loading in major histocompatibility complex class II vesicles. J. Exp. Med 181, 1729–1741
    OpenUrlAbstract/FREE Full Text
    1. Angelisova, P.,
    2. Hilgert, I. and
    3. Horejsi, V.
    (1994). Association of four antigens of the tetraspans family (CD37, CD53, TAPA-1, and R2/C33) with MHC class II glycoproteins. Immunogenetics 39, 249–256
    OpenUrlPubMedWeb of Science
    1. Arnold, P. Y. and
    2. Mannie, M. D.
    (1999). Vesicles bearing MHC class II molecules mediate transfer of antigen from antigen-presenting cells to CD4+ T cells. Eur. J. Immunol 29, 1363–1373
    OpenUrlCrossRefPubMedWeb of Science
    1. Bakke, O. and
    2. Nordeng, T. W.
    (1999). Intracellular traffic to compartments for MHC class II peptide loading: signals for endosomal and polarized sorting. Immunol. Rev. 172, 171–187
    OpenUrlCrossRefPubMedWeb of Science
    1. Berditchevski, F.,
    2. Tolias, K. F.,
    3. Wong, K.,
    4. Carpenter, C. L. and
    5. Hemler, M. E.
    (1997). A novel link between integrins, transmembrane-4 superfamily proteins (CD63 and CD81), and phosphatidylinositol 4-kinase. J. Biol. Chem 272, 2595–2598
    OpenUrlAbstract/FREE Full Text
    1. Bock, J. B. and
    2. Scheller, R. H.
    (1999). SNARE proteins mediate lipid bilayer fusion. Proc. Nat. Acad. Sci. USA 96, 12227–12229
    OpenUrlFREE Full Text
    1. Callahan, G. N.,
    2. Ferrone, S.,
    3. Poulik, M. D.,
    4. Reisfeld, R. A. and
    5. Klein, J.
    (1976). Characterization of Ia antigens in mouse serum. J. Immunol 117, 1351–1355
    OpenUrlAbstract/FREE Full Text
    1. Casciola-Rosen, L.,
    2. Rosen, A.,
    3. Petri, M. and
    4. Schlissel, M.
    (1996). Surface blebs on apoptotic cells are sites of enhanced procoagulant activity: implications for coagulation events and antigenic spread in systemic lupus erythematosus. Proc. Nat. Acad. Sci. USA 93, 1624–1629
    OpenUrlAbstract/FREE Full Text
    1. Davis, J. Q.,
    2. Dansereau, D.,
    3. Johnstone, R. M. and
    4. Bennett, V.
    (1986). Selective externalization of an ATP-binding protein structurally related to the clathrin-uncoating ATPase/heat shock protein in vesicles containing terminal transferrin receptors during reticulocyte maturation. J. Biol. Chem 261, 15368–15371
    OpenUrlAbstract/FREE Full Text
    1. Denzer, K.,
    2. van Eijk, M.,
    3. Kleijmeer, M. J.,
    4. Jakobson, E.,
    5. de Groot, C. and
    6. Geuze, H. J.
    (2000). Follicular dendritic cells carry MHC class II-expressing microvesicles at their surface. J. Immunol 165, 1259–1265
    OpenUrlAbstract/FREE Full Text
    1. Emerson, S. G. and
    2. Cone, R. E.
    (1979). Turnover and shedding of Ia antigens by murine spleen cells in culture. J. Immunol 122, 892–899
    OpenUrlAbstract/FREE Full Text
    1. Emerson, S. G. and
    2. Cone, R. E.
    (1981). I-Kk and H-2Kk antigens are shed as supramolecular particles in association with membrane lipids. J. Immunol 127, 482–486
    OpenUrlAbstract
    1. Escola, J. M.,
    2. Kleijmeer, M. J.,
    3. Stoorvogel, W.,
    4. Griffith, J. M.,
    5. Yoshie, O. and
    6. 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
    OpenUrlAbstract/FREE Full Text
    1. Faigle, W.,
    2. Raposo, G.,
    3. Tenza, D.,
    4. Pinet, V.,
    5. Vogt, A. B.,
    6. Kropshofer, H.,
    7. Fischer, A.,
    8. de Saint-Basile, G. and
    9. Amigorena, S.
    (1998). Deficientpeptide loading and MHC class II endosomal sorting in a human genetic immunodeficiency disease: the Chediak-Higashi syndrome. J. Cell Biol 141, 1121–1134
    OpenUrlAbstract/FREE Full Text
    1. Felder, S.,
    2. Miller, K.,
    3. Moehren, G.,
    4. Ullrich, A.,
    5. Schlessinger, J. and
    6. Hopkins, C. R.
    (1990). Kinase activity controls the sorting of the epidermal growth factor receptor within the multivesicular body. Cell 61, 623–634
    OpenUrlCrossRefPubMedWeb of Science
    1. Fernandez-Borja, M.,
    2. Wubbolts, R.,
    3. Calafat, J.,
    4. Janssen, H.,
    5. Divecha, N.,
    6. Dusseljee, S. and
    7. Neefjes, J.
    (1999). Multivesicular body morphogenesis requires phosphatidyl-inositol 3-kinase activity. Curr. Biol 9, 55–58
    OpenUrlCrossRefPubMedWeb of Science
    1. Fitter, S.,
    2. Sincock, P. M.,
    3. Jolliffe, C. N. and
    4. Ashman, L. K.
    (1999). Transmembrane 4 superfamily protein CD151 (PETA-3) associates with beta1 and alphaIIbbeta3 integrins in haemopoietic cell lines and modulates cell-cell adhesion. Biochem. J 338, 61–70
    OpenUrlAbstract/FREE Full Text
    1. Flamand, V.,
    2. Sornasse, T.,
    3. Thielemans, K.,
    4. Demanet, C.,
    5. Bakkus, M.,
    6. Bazin, H.,
    7. Tielemans, F.,
    8. Leo, O.,
    9. Urbain, J. and
    10. Moser, M.
    (1994). Murine dendritic cells pulsed in vitro with tumor antigen induce tumor resistance in vivo. Eur. J. Immunol 24, 605–610
    OpenUrlCrossRefPubMedWeb of Science
    1. Fox, J. E.
    (1994). Shedding of adhesion receptors from the surface of activated platelets. Blood Coagul. Fibrinolysis 5, 291–304
    OpenUrlCrossRefPubMedWeb of Science
    1. Futter, C. E.,
    2. Felder, S.,
    3. Schlessinger, J.,
    4. Ullrich, A. and
    5. Hopkins, C. R.
    (1993). Annexin I is phosphorylated in the multivesicular body during the processing of the epidermal growth factor receptor. J. Cell Biol 120, 77–83
    OpenUrlAbstract/FREE Full Text
    1. Futter, C. E.,
    2. Pearse, A.,
    3. Hewlett, L. J. and
    4. Hopkins, C. R.
    (1996). Multivesicular endosomes containing internalized EGF-EGF receptor complexes mature and then fuse directly with lysosomes. J. Cell Biol 132, 1011–1023
    OpenUrlAbstract/FREE Full Text
    1. Germain, R. N. and
    2. Margulies, D. H.
    (1993). The biochemistry and cell biology of antigen processing and presentation. Annu. Rev. Immunol 11, 403–450
    OpenUrlCrossRefPubMedWeb of Science
    1. Geuze, H. J.
    (1998). The role of endosomes and lysosomes in MHC class II functioning. Immunol. Today 19, 282–287
    OpenUrlCrossRefPubMedWeb of Science
    1. Grabbe, S.,
    2. Bruvers, S.,
    3. Gallo, R. L.,
    4. Knisely, T. L.,
    5. Nazareno, R. and
    6. Granstein, R. D.
    (1991). Tumor antigen presentation by murine epidermal cells. J. Immunol 146, 3656–3661
    OpenUrlAbstract/FREE Full Text
    1. Gray, D.,
    2. Kosco, M. and
    3. Stockinger, B.
    (1991). Novel pathways of antigen presentation for the maintenance of memory. Int. Immunol 3, 141–148
    OpenUrlAbstract/FREE Full Text
    1. Griffiths, G. M. and
    2. Argon, Y.
    (1995). Structure and biogenesis of lytic granules. Curr. Top. Microbiol. Immunol 198, 39–58
    OpenUrlPubMed
    1. Gromme, M.,
    2. Uytdehaag, F. G.,
    3. Janssen, H.,
    4. Calafat, J.,
    5. van Binnendijk, R. S.,
    6. Kenter, M. J.,
    7. Tulp, A.,
    8. Verwoerd, D. and
    9. Neefjes, J.
    (1999). Recycling MHC class I molecules and endosomal peptide loading. Proc. Nat. Acad. Sci. USA 96, 10326–10331
    OpenUrlAbstract/FREE Full Text
    1. Gruenberg, J.,
    2. Griffiths, G. and
    3. Howell, K. E.
    (1989). Characterization of the early endosome and putative endocytic carrier vesicles in vivo and with an assay of vesicle fusion in vitro. J. Cell Biol 108, 1301–1316
    OpenUrlAbstract/FREE Full Text
    1. Gruenberg, J. and
    2. Maxfield, F. R.
    (1995). Membrane transport in the endocytic pathway. Curr. Opin. Cell Biol 7, 552–563
    OpenUrlCrossRefPubMedWeb of Science
    1. Guo, Z.,
    2. Turner, C. and
    3. Castle, D.
    (1998). Relocation of the t-SNARE SNAP-23 from lamellipodia-like cell surface projections regulates compound exocytosis in mast cells. Cell 94, 537–548
    OpenUrlCrossRefPubMedWeb of Science
    1. Hammond, C.,
    2. Denzin, L. K.,
    3. Pan, M.,
    4. Griffith, J. M.,
    5. Geuze, H. J. and
    6. Cresswell, P.
    (1998). The tetraspan protein CD82 is a resident of MHC class II compartments where it associates with HLA-DR,DM, and DO molecules. J. Immunol 161, 3282–3291
    OpenUrlAbstract/FREE Full Text
    1. Harding, C.,
    2. Heuser, J. and
    3. Stahl, P.
    (1983). Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J. Cell Biol 97, 329–339
    OpenUrlAbstract/FREE Full Text
    1. Harding, C.,
    2. Heuser, J. and
    3. Stahl, P.
    (1984). Endocytosis and intracellular processing of transferrin and colloidal gold-transferrin in rat reticulocytes: demonstration of a pathway for receptor shedding. Eur. J. Cell Biol 35, 256–263
    OpenUrlPubMedWeb of Science
    1. Hart, D. N.
    (1997). Dendritic cells: unique leukocyte populations which control the primary immune response. Blood 90, 3245–3287
    OpenUrlFREE Full Text
    1. Heijnen, H. F. G.,
    2. Schiel, A. E.,
    3. Fijnheer, R.,
    4. Geuze, H. J. and
    5. Sixma, J. J.
    (1999). Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. Blood 94, 3791–3799
    OpenUrlAbstract/FREE Full Text
    1. Hibi, T.,
    2. Hirashima, N. and
    3. Nakanishi, M.
    (2000). Rat basophilic leukemia cells express syntaxin-3 and VAMP-7 in granule membranes. Biochem. Biophys. Res. Commun 271, 36–41
    OpenUrlCrossRefPubMedWeb of Science
    1. Hirsch, J. G.,
    2. Fedorko, M. E. and
    3. Cohn, Z. A.
    (1968). Vesicle fusion and formation at the surface of pinocytic vacuoles in macrophages. J. Cell Biol 38, 629–632
    OpenUrlFREE Full Text
    1. Hoffman, M.,
    2. Monroe, D. M. and
    3. Roberts, H. R.
    (1992). Coagulation factorIXa binding to activated platelets and platelet-derived microparticles: a flow cytometric study. Thromb. Haemost 68, 74–78
    OpenUrlPubMedWeb of Science
    1. Imai, T.,
    2. Kakizaki, M.,
    3. Nishimura, M. and
    4. Yoshie, O.
    (1995). Molecular analyses of the association of CD4 with two members of the transmembrane 4 superfamily, CD81 and CD82. J. Immunol 155, 1229–1239
    OpenUrlAbstract/FREE Full Text
    1. Johnstone, R. M.,
    2. Adam, M.,
    3. Hammond, J. R.,
    4. Orr, L. and
    5. Turbide, C.
    (1987). Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J. Biol. Chem 262, 9412–9420
    OpenUrlAbstract/FREE Full Text
    1. Jondal, M.,
    2. Schirmbeck, R. and
    3. Reimann, J.
    (1996). MHC class I-restricted CTL responses to exogenous antigens. Immunity 5, 295–302
    OpenUrlCrossRefPubMedWeb of Science
    1. Kleijmeer, M. J.,
    2. Ossevoort, M. A.,
    3. van Veen, C. J.,
    4. van Hellemond, J. J.,
    5. Neefjes, J. J.,
    6. Kast, W. M.,
    7. Melief, C. J. and
    8. Geuze, H. J.
    (1995). MHC class II compartments and the kinetics of antigen presentation in activated mouse spleen dendritic cells. J. Immunol 154, 5715–5724
    OpenUrlAbstract
    1. Kleijmeer, M. J.,
    2. Morkowski, S.,
    3. Griffith, J. M.,
    4. Rudensky, A. Y. and
    5. Geuze, H. J.
    (1997). Major histocompatibility complex class II compartments in human and mouse B lymphoblasts represent conventional endocytic compartments. J. Cell Biol 139, 639–649
    OpenUrlAbstract/FREE Full Text
    1. Kobayashi, T.,
    2. Stang, E.,
    3. Fang, K. S.,
    4. de Moerloose, P.,
    5. Parton, R. G. and
    6. Gruenberg, J.
    (1998). A lipid associated with the antiphospholipid syndrome regulates endosome structure and function. Nature 392, 193–197
    OpenUrlCrossRefPubMedWeb of Science
    1. Lagaudriere-Gesbert, C.,
    2. Lebel-Binay, S.,
    3. Wiertz, E.,
    4. Ploegh, H. L.,
    5. Fradelizi, D. and
    6. Conjeaud, H.
    (1997). The tetraspanin protein CD82 associates with both free HLA class I heavy chain and heterodimeric beta 2-microglobulin complexes. J. Immunol 158, 2790–2797
    OpenUrlAbstract
    1. Lindhout, E.,
    2. Koopman, G.,
    3. Pals, S. T. and
    4. de Groot, C.
    (1997). Triple check for antigen specificity of B cells during germinal centre reactions. Immunol. Today 18, 573–577
    OpenUrlCrossRefPubMedWeb of Science
    1. Liu, S. H.,
    2. Marks, M. S. and
    3. Brodsky, F. M.
    (1998). A dominant-negative clathrin mutant differentially affects trafficking of molecules with distinct sorting motifs in the class II major histocompatibility complex (MHC) pathway. J. Cell Biol 140, 1023–1037
    OpenUrlAbstract/FREE Full Text
    1. Liu, Y. J.,
    2. Grouard, G.,
    3. de Bouteiller, O. and
    4. Banchereau, J.
    (1996). Follicular dendritic cells and germinal centers. Int. Rev. Cytol 166, 139–179
    OpenUrlCrossRefPubMedWeb of Science
    1. Luykx-de Bakker, S. A.,
    2. de Gruijl, T. D.,
    3. Scheper, R. J.,
    4. Wagstaff, J. and
    5. Pinedo, H. M.
    (1999). Dendritic cells: a novel therapeutic modality. Ann. Oncol 10, 21–27
    OpenUrlFREE Full Text
    1. Luzio, J. P.,
    2. Rous, B. A.,
    3. Bright, N. A.,
    4. Pryor, P. R.,
    5. Mullock, B. M. and
    6. Piper, R. C.
    (2000). Lysosome-endosome fusion and lysosome biogenesis. J. Cell Sci 113, 1515–1524
    OpenUrlAbstract/FREE Full Text
    1. Martinez, I.,
    2. Chakrabarti, S.,
    3. Hellevik, T.,
    4. Morehead, J.,
    5. Fowler, K. and
    6. Andrews, N. W.
    (2000). Synaptotagmin VII regulates Ca(2+)-dependent exocytosis of lysosomes in fibroblasts. J. Cell Biol 148, 1141–1149
    OpenUrlAbstract/FREE Full Text
    1. Mathew, A.,
    2. Bell, A. and
    3. Johnstone, R. M.
    (1995). Hsp-70 is closely associated with the transferrin receptor in exosomes from maturing reticulocytes. Biochem. J 308, 823–830
    OpenUrlAbstract/FREE Full Text
    1. Mellman, I.
    (1996). Endocytosis and molecular sorting. Annu. Rev. Cell Dev. Biol 12, 575–625
    OpenUrlCrossRefPubMedWeb of Science
    1. Miyazaki, Y.,
    2. Nomura, S.,
    3. Miyake, T.,
    4. Kagawa, H.,
    5. Kitada, C.,
    6. Taniguchi, H.,
    7. Komiyama, Y.,
    8. Fujimura, Y.,
    9. Ikeda, Y. and
    10. Fukuhara, S.
    (1996). High shear stress can initiate both platelet aggregation and shedding of procoagulant containing microparticles. Blood 88, 3456–3464
    OpenUrlAbstract/FREE Full Text
    1. Mullock, B. M.,
    2. Bright, N. A.,
    3. Fearon, C. W.,
    4. Gray, S. R. and
    5. Luzio, J. P.
    (1998). Fusion of lysosomes with late endosomes produces a hybrid organelle of intermediate density and is NSF dependent. J. Cell Biol 140, 591–601
    OpenUrlAbstract/FREE Full Text
    1. Nakagawa, T. Y. and
    2. Rudensky, A. Y.
    (1999). The role of lysosomal proteinases in MHC class II-mediated antigen processing and presentation. Immunol. Rev. 172, 121–129
    OpenUrlCrossRefPubMedWeb of Science
    1. Nijman, H. W.,
    2. Kleijmeer, M. J.,
    3. Ossevoort, M. A.,
    4. Oorschot, V. M.,
    5. Vierboom, M. P.,
    6. van de Keur, M.,
    7. Kenemans, P.,
    8. Kast, W. M.,
    9. Geuze, H. J. and
    10. Melief, C. J.
    (1995). Antigen capture and majorhistocompatibility class II compartments of freshly isolated and cultured human blood dendritic cells. J. Exp. Med 182, 163–174
    OpenUrlAbstract/FREE Full Text
    1. Odorizzi, G.,
    2. Babst, M. and
    3. Emr, S. D.
    (1998). Fab1p PtdIns(3)P 5-kinase function essential for protein sorting in the multivesicular body. Cell 95, 847–858
    OpenUrlCrossRefPubMedWeb of Science
    1. Pan, B. T. and
    2. Johnstone, R. M.
    (1983). Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: Selective externalization of the receptor. Cell 33, 967–977
    OpenUrlCrossRefPubMedWeb of Science
    1. Pan, B. T.,
    2. Teng, K.,
    3. Wu, C.,
    4. Adam, M. and
    5. Johnstone, R. M.
    (1985). Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes. J. Cell Biol 101, 942–948
    OpenUrlAbstract/FREE Full Text
    1. Peters, P. J.,
    2. Geuze, H. J.,
    3. van der Donk, H. A.,
    4. Slot, J. W.,
    5. Griffith, J. M.,
    6. Stam, N. J.,
    7. Clevers, H. C. and
    8. Borst, J.
    (1989). Molecules relevant for T cell-target cell interaction are present in cytolytic granules of human T lymphocytes. Eur. J. Immunol 19, 1469–1475
    OpenUrlCrossRefPubMedWeb of Science
    1. Peters, P. J.,
    2. Geuze, H. J.,
    3. van der Donk, H. A. and
    4. Borst, J.
    (1990). A new model for lethal hit delivery by cytotoxic T lymphocytes. Immunol. Today 11, 28–32
    OpenUrlCrossRefPubMedWeb of Science
    1. Peters, P. J.,
    2. Borst, J.,
    3. Oorschot, V.,
    4. Fukuda, M.,
    5. Krahenbuhl, O.,
    6. Tschopp, J.,
    7. Slot, J. W. and
    8. Geuze, H. J.
    (1991). Cytotoxic T lymphocyte granules are secretory lysosomes, containing both perforin and granzymes. J. Exp. Med 173, 1099–1109
    OpenUrlAbstract/FREE Full Text
    1. Peters, P. J.,
    2. Neefjes, J. J.,
    3. Oorschot, V.,
    4. Ploegh, H. L. and
    5. Geuze, H. J.
    (1991). Segregation of MHC class II molecules from MHC class I molecules in the Golgi complex for transport to lysosomal compartments. Nature 349, 669–676
    OpenUrlCrossRefPubMed
    1. Pierre, P.,
    2. Denzin, L. K.,
    3. Hammond, C.,
    4. Drake, J. R.,
    5. Amigorena, S.,
    6. Cresswell, P. and
    7. Mellman, I.
    (1996). HLA-DM is localized to conventional and unconventional MHC class II-containing endocytic compartments. Immunity 4, 229–239
    OpenUrlCrossRefPubMedWeb of Science
    1. Pond, L. and
    2. Watts, C.
    (1997). Characterization of transport of newly assembled, T cell-stimulatory MHC class II-peptide complexes from MHC class II compartments to the cell surface. J. Immunol 159, 543–553
    OpenUrlAbstract
    1. Pond, L. and
    2. Watts, C.
    (1999). Functional early endosomes are required for maturation of major histocompatibility complex class II molecules in human B lymphoblastoid cells. J. Biol. Chem 274, 18049–18054
    OpenUrlAbstract/FREE Full Text
    1. Rabesandratana, H.,
    2. Toutant, J. P.,
    3. Reggio, H. and
    4. Vidal, M.
    (1998). Decay-accelerating factor (CD55) and membrane inhibitor of reactive lysis (CD59) are released within exosomes during In vitro maturation of reticulocytes. Blood 91, 2573–2580
    OpenUrlAbstract/FREE Full Text
    1. Raposo, G.,
    2. Nijman, H. W.,
    3. Stoorvogel, W.,
    4. Leijendekker, R.,
    5. Harding, C. V.,
    6. Melief, C. J. and
    7. Geuze, H. J.
    (1996). B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med 183, 1161–1172
    OpenUrlAbstract/FREE Full Text
    1. Raposo, G.,
    2. Tenza, D.,
    3. Mecheri, S.,
    4. Peronet, R.,
    5. Bonnerot, C. and
    6. Desaymard, C.
    (1997). Accumulation of Major Histocompatibility Complex Class II molecules in mast cell secretory granules and their release upon degranulation. Mol. Biol. Cell 8, 2631–2645
    OpenUrlAbstract/FREE Full Text
    1. Rieu, S.,
    2. Geminard, C.,
    3. Rabesandratana, H.,
    4. Sainte-Marie, J. and
    5. Vidal, M.
    (2000). Exosomes released during reticulocyte maturation bind to fibronectin via integrin4 1. Eur. J. Biochem 267, 583–590
    OpenUrlPubMedWeb of Science
    1. Rodriguez, A.,
    2. Webster, P.,
    3. Ortego, J. and
    4. Andrews, N. W.
    (1997). Lysosomes behave as Ca2+-regulated exocytic vesicles in fibroblasts and epithelial cells. J. Cell Biol 137, 93–104
    OpenUrlAbstract/FREE Full Text
    1. Rothman, J. E.
    (1994). Mechanisms of intracellular protein transport. Nature 372, 55–63
    OpenUrlCrossRefPubMedWeb of Science
    1. Rubinstein, E.,
    2. Le Naour, F.,
    3. Lagaudriere-Gesbert, C.,
    4. Billard, M.,
    5. Conjeaud, H. and
    6. Boucheix, C.
    (1996). CD9, CD63, CD81, and CD82 are components of a surface tetraspan network connected to HLA-DR and VLA integrins. Eur. J. Immunol 26, 2657–2665
    OpenUrlCrossRefPubMedWeb of Science
    1. Sallusto, F.,
    2. Cella, M.,
    3. Danieli, C. and
    4. Lanzavecchia, A.
    (1995). Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatibility complex class II compartment: downregulation by cytokines and bacterial products. J. Exp. Med 182, 389–400
    OpenUrlAbstract/FREE Full Text
    1. Shimizu, J.,
    2. Suda, T.,
    3. Yoshioka, T.,
    4. Kosugi, A.,
    5. Fujiwara, H. and
    6. Hamaoka, T.
    (1989). Induction of tumor-specific in vivo protective immunity by immunization with tumor antigen-pulsed antigen-presenting cells. J. Immunol 142, 1053–1059
    OpenUrlAbstract/FREE Full Text
    1. Sims, P. J.,
    2. Wiedmer, T.,
    3. Esmon, C. T.,
    4. Weiss, H. J. and
    5. Shattil, S. J.
    (1989). Assembly of the platelet prothrombinase complex is linked to vesiculationofthe platelet plasma membrane. Studies in Scott syndrome: an isolated defectin platelet procoagulant activity. J. Biol. Chem 264, 17049–17057
    OpenUrlAbstract/FREE Full Text
    1. Stinchcombe, J. C. and
    2. Griffiths, G. M.
    (1999). Regulated secretion from hemopoietic cells. J. Cell Biol 147, 1–5
    OpenUrlFREE Full Text
    1. Stuart, M. C.,
    2. Bevers, E. M.,
    3. Comfurius, P.,
    4. Zwaal, R. F.,
    5. Reutelingsperger, C. P. and
    6. Frederik, P. M.
    (1995). Ultrastructural detection of surface exposed phosphatidylserine on activated blood platelets. Thromb. Haemost 74, 1145–1151
    OpenUrlPubMedWeb of Science
    1. Tew, J. G.,
    2. Burton, G. F.,
    3. Kupp, L. I. and
    4. Szakal, A.
    (1993). Follicular dendritic cells in germinal center reactions. Adv. Exp. Med. Biol 329, 461–465
    OpenUrlCrossRefPubMed
    1. Thery, C.,
    2. Regnault, A.,
    3. Garin, J.,
    4. Wolfers, J.,
    5. Zitvogel, L.,
    6. Ricciardi-Castagnoli, P.,
    7. Raposo, G. and
    8. Amigorena, S.
    (1999). Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73. J. Cell Biol 147, 599–610
    OpenUrlAbstract/FREE Full Text
    1. Timmerman, J. M. and
    2. Levy, R.
    (1999). Dendritic cell vaccines for cancer immunotherapy. Annu. Rev. Med 50, 507–529
    OpenUrlCrossRefPubMedWeb of Science
    1. Townsend, A. and
    2. Bodmer, H.
    (1989). Antigen recognition by class I-restricted T lymphocytes. Annu. Rev. Immunol 7, 601–624
    OpenUrlCrossRefPubMedWeb of Science
    1. Turley, S. J.,
    2. Inaba, K.,
    3. Garret, W. S.,
    4. Ebersold, M.,
    5. Unternaehrer, J.,
    6. Steinman, R. M. and
    7. Mellman, I.
    (2000). Transport of peptide-MHC class II complexes in developing dendritic cells. Science 288, 522–527
    OpenUrlAbstract/FREE Full Text
    1. Udono, H. and
    2. Srivastava, P. K.
    (1993). Heat shock protein 70-associated peptides elicit specific cancer immunity. J. Exp. Med 178, 1391–1396
    OpenUrlAbstract/FREE Full Text
    1. van Bockxmeer, F. M. and
    2. Morgan, E. H.
    (1979). Transferrin receptors during rabbit reticulocyte maturation. Biochim. Biophys. Acta 584, 76–83
    OpenUrlCrossRefPubMed
    1. van Deurs, B.,
    2. Holm, P. K.,
    3. Kayser, L.,
    4. Sandvig, K. and
    5. Hansen, S. H.
    (1993). Multivesicular bodies in HEp-2 cells are maturing endosomes. Eur. J. Cell Biol 61, 208–224
    OpenUrlPubMedWeb of Science
    1. Vidal, M.,
    2. Sainte-Marie, J.,
    3. Philippot, J. R. and
    4. Bienvenue, A.
    (1989). Asymmetric distribution of phospholipids in the membrane of vesicles released during in vitro maturation of guinea pig reticulocytes: evidence precluding a role for ‘aminophospholipid translocase’. J. Cell Physiol 140, 455–462
    OpenUrlCrossRefPubMedWeb of Science
    1. Vidal, M. J. and
    2. Stahl, P. D.
    (1993). The small GTP-binding proteins Rab4 and ARF are associated with released exosomes during reticulocyte maturation. Eur. J. Cell Biol 60, 261–267
    OpenUrlPubMed
    1. Vidal, M.,
    2. Mangeat, P. and
    3. Hoekstra, D.
    (1997). Aggregation reroutes molecules from a recycling to a vesicle-mediated secretion pathway during reticulocyte maturation. J. Cell Sci 110, 1867–1877
    OpenUrlAbstract/FREE Full Text
    1. Villadangos, J. A.,
    2. Bryant, R. A. R.,
    3. Deussing, J.,
    4. Driessen, C.,
    5. Lennon-Dumenil, A.-M.,
    6. Riese, R. J.,
    7. Roth, W.,
    8. Saftig, P.,
    9. Shi, G.-P.,
    10. Chapman, H. A.,
    11. Peters, C. and
    12. Ploegh, H. L.
    (1999). : Proteases involved in MHC class II antigen presentation. Immunol. Rev. 172, 109–120
    OpenUrlCrossRefPubMedWeb of Science
    1. Wherrett, J. R. and
    2. Huterer, S.
    (1972). Enrichment of bis-(monoacylglyceryl) phosphate in lysosomes from rat liver. J. Biol. Chem 247, 4114–4120
    OpenUrlAbstract/FREE Full Text
    1. Wolf, P. R. and
    2. Ploegh, H. L.
    (1995). How MHC class II molecules acquire peptide cargo: biosynthesis and trafficking through the endocytic pathway. Annu. Rev. Cell Dev. Biol 11, 267–306
    OpenUrlCrossRefPubMedWeb of Science
    1. Wubbolts, R.,
    2. Fernandez-Borja, M.,
    3. Oomen, L.,
    4. Verwoerd, D.,
    5. Janssen, H.,
    6. Calafat, J.,
    7. Tulp, A.,
    8. Dusseljee, S. and
    9. Neefjes, J.
    (1996). Direct vesicular transport of MHC class II molecules from lysosomal structures to the cell surface. J. Cell Biol 135, 611–622
    OpenUrlAbstract/FREE Full Text
    1. Wubbolts, R. and
    2. Neefjes, J.
    (1999). Intracellular transport and peptide loading of MHC class II molecules: regulation by chaperones and motors. Immunol. Rev. 172, 189–208
    OpenUrlCrossRefPubMed
    1. Wurmser, A. E. and
    2. Emr, S. D.
    (1998). Phosphoinositide signaling and turnover: PtdIns(3)P, a regulator of membrane traffic, is transported to the vacuole and degraded by a process that requires lumenal vacuolar hydrolase activities. EMBO J 17, 4930–4942
    OpenUrlAbstract
    1. Zwaal, R. F.,
    2. Bevers, E. M.,
    3. Comfurius, P.,
    4. Rosing, J.,
    5. Tilly, R. H. and
    6. Verhallen, P. F.
    (1989). Loss of membrane phospholipid asymmetry during activation of bloodplatelets and sickled red cells; mechanisms and physiological significance. Mol. Cell Biochem 91, 23–31
    OpenUrlCrossRefPubMedWeb of Science
Back to top

 Download PDF

Email
Journal Article
Exosome: from internal vesicle of the multivesicular body to intercellular signaling device
K. Denzer, M.J. Kleijmeer, H.F. Heijnen, W. Stoorvogel, H.J. Geuze
Journal of Cell Science 2000 113: 3365-3374;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
Citation Tools
Alerts

Article navigation

Other journals from The Company of Biologists

Advertisement

Follow us on Instagram

Cell science is bursting with beautiful images and over on Instagram, we’re showing them off! Find both JCS and FocalPlane on Instagram for stories and techniques across cell biology.

An interview with Derek Walsh

Professor Derek Walsh is the guest editor of our new special issue Cell Biology of Host-Pathogen Interactions. In an interview, Derek tells us about his work in the field of DNA viruses, the impact of the pandemic on virology and what his role as Guest Editor taught him.

How to improve your scientific writing

"If you are a scientist and you want to succeed, you must become a writer."

How do scientists become master storytellers? We called on our journal Editors, proofreaders and contributors to our community sites for their advice on how to improve your scientific writing.

Meet the preLighters: Jennifer Ann Black

Following the theme of our latest special issue, postdoc Jennifer Ann Black studies replication stress and genome plasticity in Leishmania in Professor Luiz Tosi’s lab in Sao Paolo. We caught up with Jenn (virtually) to hear about her relocation to Brazil mid-pandemic, her research on parasites and what she enjoys about ‘preLighting’.

In our special issue, Chandrakar et al. and Rosazza et al. present their latest work on Leishmania.

Mole – The Corona Files

“There are millions of people around the world who continue to believe that the Terrible Pandemic is a hoax.”

Mole continues to offer his wise words to researchers on how to manage during the COVID-19 pandemic.

JCS and COVID-19

For more information on measures Journal of Cell Science is taking to support the community during the COVID-19 pandemic, please see here.

If you have any questions or concerns, please do not hestiate to contact the Editorial Office.