Exosomes in developmental signalling

Development (Cambridge)

Volumn 143, Issue 14, 2016, Pages 2482-2493

  McGough, Ian John ^a   Vincent, Jean Paul ^a  

^a THE FRANCIS CRICK INSTITUTE   (United Kingdom)

Author keywords

Exosomes; Hedgehog; Signalling; WNT

Indexed keywords

ADENOSINE TRIPHOSPHATASE; ESCRT PROTEIN; GUANOSINE TRIPHOSPHATASE; SNARE PROTEIN; SONIC HEDGEHOG PROTEIN; WNT PROTEIN;

ARTICLE; BIOGENESIS; CARCINOGENESIS; CELL MEMBRANE; EXOSOME; HUMAN; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; UBIQUITINATION; ANIMAL; BIOLOGICAL MODEL; GROWTH, DEVELOPMENT AND AGING; METABOLISM; PATHOLOGY;

ANIMALS; CARCINOGENESIS; CELL MEMBRANE; EXOSOMES; GROWTH AND DEVELOPMENT; HUMANS; MODELS, BIOLOGICAL; SIGNAL TRANSDUCTION;

EID: 84978706266     PISSN: 09501991     EISSN: 14779129     Source Type: Journal    
DOI: 10.1242/dev.126516     Document Type: Article

References (151)

1. Agromayor, M. and Martin-Serrano, J. (2006). Interaction of AMSH with ESCRT-III and deubiquitination of endosomal cargo. J. Biol. Chem. 281, 23083-23091.
2. Alexandre, C.,Baena-Lopez, A. and Vincent, J.-P. (2014). Patterning and growth control by membrane-tethered Wingless. Nature 505, 180-185.
3. Antonucci, F.,Turola, E.,Riganti, L.,Caleo, M.,Gabrielli, M.,Perrotta, C.,Novellino, L.,Clementi, E.,Giussani, P.,Viani, P. et al. (2012). Microvesicles released from microglia stimulate synaptic activity via enhanced sphingolipid metabolism. EMBO J. 31, 1231-1240.
4. Avanesov, A.,Honeyager, S. M.,Malicki, J. and Blair, S. S. (2012). The role of glypicans in Wnt inhibitory factor-1 activity and the structural basis of Wif1’s effects on Wnt and Hedgehog signaling. PLoS Genet. 8, e1002503.
5. Babst, M.,Katzmann, D. J.,Estepa-Sabal, E. J.,Meerloo, T. and Emr, S. D. (2002). Escrt-III: an endosome-associated heterooligomeric protein complex required for mvb sorting. Dev. Cell 3, 271-282.
6. Baietti, M. F.,Zhang, Z.,Mortier, E.,Melchior, A.,Degeest, G.,Geeraerts, A.,Ivarsson, Y.,Depoortere, F.,Coomans, C.,Vermeiren, E. et al. (2012). Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat. Cell Biol. 14, 677-685.
7. Bakhti, M.,Winter, C. and Simons, M. (2011). Inhibition of myelin membrane sheath formation by oligodendrocyte-derived exosome-like vesicles. J. Biol. Chem. 286, 787-796.
8. Bänziger, C.,Soldini, D.,Schütt, C.,Zipperlen, P.,Hausmann, G. and Basler, K. (2006). Wntless, a conserved membrane protein dedicated to the secretion of Wnt proteins from signaling cells. Cell 125, 509-522.
9. Bartscherer, K.,Pelte, N.,Ingelfinger, D. and Boutros, M. (2006). Secretion of Wnt ligands requires Evi, a conserved transmembrane protein. Cell 125, 523-533.
10. Beckett, K.,Monier, S.,Palmer, L.,Alexandre, C.,Green, H.,Bonneil, E.,Raposo, G.,Thibault, P.,Le Borgne, R. and Vincent, J.-P. (2013). Drosophila S2 cells secrete wingless on exosome-like vesicles but the wingless gradient forms independently of exosomes. Traffic 14, 82-96.
11. Bianco, F.,Perrotta, C.,Novellino, L.,Francolini, M.,Riganti, L.,Menna, E.,Saglietti, L.,Schuchman, E. H.,Furlan, R.,Clementi, E. et al. (2009). Acid sphingomyelinase activity triggers microparticle release from glial cells. EMBO J. 28, 1043-1054.
12. Bilodeau, P. S.,Urbanowski, J. L.,Winistorfer, S. C. and Piper, R. C. (2002). The Vps27p Hse1p complex binds ubiquitin and mediates endosomal protein sorting. Nat. Cell Biol. 4, 534-539.
13. Bischoff, M.,Gradilla, A.-C.,Seijo, I.,Andrés, G.,Rodríguez-Navas, C.,González-Méndez, L. and Guerrero, I. (2013). Cytonemes are required for the establishment of a normal Hedgehog morphogen gradient in Drosophila epithelia. Nat. Cell Biol. 15, 1269-1281.
14. Bissig, C. and Gruenberg, J. (2014). ALIX and the multivesicular endosome: ALIX in Wonderland. Trends Cell Biol. 24, 19-25.
15. Brugger, B.,Glass, B.,Haberkant, P.,Leibrecht, I.,Wieland, F. T. and Krausslich, H.-G. (2006). The HIV lipidome: a raft with an unusual composition. Proc. Natl. Acad. Sci. USA 103, 2641-2646.
16. Burke, R.,Nellen, D.,Bellotto, M.,Hafen, E.,Senti, K.-A.,Dickson, B. J. and Basler, K. (1999). Dispatched, a novel sterol-sensing domain protein dedicated to the release of cholesterol-modified hedgehog from signaling cells. Cell 99, 803-815.
17. Buschow, S. I.,van Balkom, B. W. M.,Aalberts, M.,Heck, A. J. R.,Wauben, M. and Stoorvogel, W. (2010). MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis. Immunol. Cell Biol. 88, 851-856.
18. Cai, H.,Reinisch, K. and Ferro-Novick, S. (2007). Coats, tethers, Rabs, and SNAREs work together to mediate the intracellular destination of a transport vesicle. Dev. Cell 12, 671-682.
19. Callejo, A.,Torroja, C.,Quijada, L. and Guerrero, I. (2006). Hedgehog lipid modifications are required for Hedgehog stabilization in the extracellular matrix. Development 133, 471-483.
20. Callejo, A.,Bilioni, A.,Mollica, E.,Gorfinkiel, N.,Andres, G.,Ibanez, C.,Torroja, C.,Doglio, L.,Sierra, J. and Guerrero, I. (2011). Dispatched mediates Hedgehog basolateral release to form the long-range morphogenetic gradient in the Drosophila wing disk epithelium. Proc. Natl. Acad. Sci. USA 108, 12591-12598.
21. Campbell, R. M. and Peterson, A. C. (1993). Expression of a lacZ transgene reveals floor plate cell morphology and macromolecular transfer to commissural axons. Development 119, 1217-1228.
22. Chamoun, Z.,Mann, R. K.,Nellen, D.,von Kessler, D. P.,Bellotto, M.,Beachy, P. A. and Basler, K. (2001). Skinny hedgehog, an acyltransferase required for palmitoylation and activity of the hedgehog signal. Science 293, 2080-2084.
23. Chaput, N. and Thery, C. (2011). Exosomes: immune properties and potential clinical implementations. Semin. Immunopathol. 33, 419-440.
24. Chen, M.-H.,Li, Y.-J.,Kawakami, T.,Xu, S.-M. and Chuang, P.-T. (2004). Palmitoylation is required for the production of a soluble multimeric Hedgehog protein complex and long-range signaling in vertebrates. Genes Dev. 18, 641-659.
25. Chiaruttini, N.,Redondo-Morata, L.,Colom, A.,Humbert, F.,Lenz, M.,Scheuring, S. and Roux, A. (2015). Relaxation of loaded ESCRT-III spiral springs drives membrane deformation. Cell 163, 866-879.
26. Clayton, A. and Mason, M. D. (2009). Exosomes in tumour immunity. Curr. Oncol. 16, 46-49.
27. Clevers, H.,Loh, K. M. and Nusse, R. (2014). Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control. Science 346, 1248012.
28. Cocucci, E. and Meldolesi, J. (2015). Ectosomes and exosomes: shedding the confusion between extracellular vesicles. Trends Cell Biol. 25, 364-372.
29. Coleman, B. M. and Hill, A. F. (2015). Extracellular vesicles–Their role in the packaging and spread of misfolded proteins associated with neurodegenerative diseases. Semin. Cell Dev. Biol. 40, 89-96.
30. Costa-Silva, B.,Aiello, N. M.,Ocean, A. J.,Singh, S.,Zhang, H.,Thakur, B. K.,Becker, A.,Hoshino, A.,Mark, M. T.,Molina, H. et al. (2015). Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver. Nat. Cell Biol. 17, 816-826.
31. D’Angelo, G.,Matusek, T.,Pizette, S. and Thérond, P. P. (2015). Endocytosis of Hedgehog through dispatched regulates long-range signaling. Dev. Cell 32, 290-303.
32. Dawber, R. J.,Hebbes, S.,Herpers, B.,Docquier, F. and van den Heuvel, M. (2005). Differential range and activity of various forms of the Hedgehog protein. BMC Dev. Biol. 5, 21.
33. Demory Beckler, M.,Higginbotham, J. N.,Franklin, J. L.,Ham, A.-J.,Halvey, P. J.,Imasuen, I. E.,Whitwell, C.,Li, M.,Liebler, D. C. and Coffey, R. J. (2013). Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS. Mol. Cell. Proteomics 12, 343-355.
34. Dores, M. R.,Chen, B.,Lin, H.,Soh, U. J. K.,Paing, M. M.,Montagne, W. A.,Meerloo, T. and Trejo, J. (2012). ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting. J. Cell Biol. 197, 407-419.
35. Echelard, Y.,Epstein, D. J.,St-Jacques, B.,Shen, L.,Mohler, J.,McMahon, J. A. and McMahon, A. P. (1993). Sonic hedgehog, a member of a family of putative signaling molecules, is implicated in the regulation of CNS polarity. Cell 75, 1417-1430.
36. Edgar, J. R.,Eden, E. R. and Futter, C. E. (2014). Hrs- and CD63-dependent competing mechanisms make different sized endosomal intraluminal vesicles. Traffic 15, 197-211.
37. Emmanouilidou, E.,Melachroinou, K.,Roumeliotis, T.,Garbis, S. D.,Ntzouni, M.,Margaritis, L. H.,Stefanis, L. and Vekrellis, K. (2010). Cell-produced alphasynuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival. J. Neurosci. 30, 6838-6851.
38. Fader, C. M.,Sánchez, D. G.,Mestre, M. B. and Colombo, M. I. (2009). TI-VAMP/ VAMP7 and VAMP3/cellubrevin: two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways. Biochim. Biophys. Acta 1793, 1901-1916.
39. Farin, H. F.,Jordens, I.,Mosa, M. H.,Basak, O.,Korving, J.,Tauriello, D. V. F.,de Punder, K.,Angers, S.,Peters, P. J.,Maurice, M. M. et al. (2016). Visualization of a short-range Wnt gradient in the intestinal stem-cell niche. Nature 530, 340-343.
40. Feiler, M. S.,Strobel, B.,Freischmidt, A.,Helferich, A. M.,Kappel, J.,Brewer, B. M.,Li, D.,Thal, D. R.,Walther, P.,Ludolph, A. C. et al. (2015). TDP-43 is intercellularly transmitted across axon terminals. J. Cell Biol. 211, 897-911.
41. Fisher, R. D.,Wang, B.,Alam, S. L.,Higginson, D. S.,Robinson, H.,Sundquist, W. I. and Hill, C. P. (2003). Structure and ubiquitin binding of the ubiquitin-interacting motif. J. Biol. Chem. 278, 28976-28984.
42. Fisher, R. D.,Chung, H.-Y.,Zhai, Q.,Robinson, H.,Sundquist, W. I. and Hill, C. P. (2007). Structural and biochemical studies of ALIX/AIP1 and its role in retrovirus budding. Cell 128, 841-852.
43. Fruhbeis, C.,Frohlich, D.,Kuo, W. P. and Kramer-Albers, E.-M. (2013). Extracellular vesicles as mediators of neuron-glia communication. Front. Cell Neurosci. 7, 182.
44. Gallet, A.,Rodriguez, R.,Ruel, L. and Therond, P. P. (2003). Cholesterol modification of hedgehog is required for trafficking and movement, revealing an asymmetric cellular response to hedgehog. Dev. Cell 4, 191-204.
45. Gallet, A.,Ruel, L.,Staccini-Lavenant, L. and Therond, P. P. (2006). Cholesterol modification is necessary for controlled planar long-range activity of Hedgehog in Drosophila epithelia. Development 133, 407-418.
46. Geminard, 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.
47. Gibbings, D. J.,Ciaudo, C.,Erhardt, M. and Voinnet, O. (2009). Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nat. Cell Biol. 11, 1143-1149.
48. Glise, B.,Miller, C. A.,Crozatier, M.,Halbisen, M. A.,Wise, S.,Olson, D. J.,Vincent, A. and Blair, S. S. (2005). Shifted, the Drosophila ortholog of Wnt inhibitory factor-1, controls the distribution and movement of Hedgehog. Dev. Cell 8, 255-266.
49. Goetz, J. A.,Singh, S.,Suber, L. M.,Kull, F. J. and Robbins, D. J. (2006). A highly conserved amino-terminal region of sonic hedgehog is required for the formation of its freely diffusible multimeric form. J. Biol. Chem. 281, 4087-4093.
50. Goodman, R. M.,Thombre, S.,Firtina, Z.,Gray, D.,Betts, D.,Roebuck, J.,Spana, E. P. and Selva, E. M. (2006). Sprinter: a novel transmembrane protein required for Wg secretion and signaling. Development 133, 4901-4911.
51. Gorfinkiel, N.,Sierra, J.,Callejo, A.,Ibañez, C. and Guerrero, I. (2005). The Drosophila ortholog of the human Wnt inhibitor factor Shifted controls the diffusion of lipid-modified Hedgehog. Dev. Cell 8, 241-253.
52. Gould, S. J. and Raposo, G. (2013). As we wait: coping with an imperfect nomenclature for extracellular vesicles. J. Extracell Vesicles 2, 20389.
53. Gradilla, A.-C.,González, E.,Seijo, I.,Andrés, G.,Bischoff, M.,González-Mendez, L.,Sánchez, V.,Callejo, A.,Ibáñez, C.,Guerra, M. et al. (2014). Exosomes as Hedgehog carriers in cytoneme-mediated transport and secretion. Nat. Commun. 5, 5649.
54. Greco, V.,Hannus, M. and Eaton, S. (2001). Argosomes: a potential vehicle for the spread of morphogens through epithelia. Cell 106, 633-645.
55. Grootjans, J. J.,Zimmermann, P.,Reekmans, G.,Smets, A.,Degeest, G.,Durr, J. and David, G. (1997). Syntenin, a PDZ protein that binds syndecan cytoplasmic domains. Proc. Natl. Acad. Sci. USA 94, 13683-13688.
56. Gross, J. C.,Chaudhary, V.,Bartscherer, K. and Boutros, M. (2012). Active Wnt proteins are secreted on exosomes. Nat. Cell Biol. 14, 1036-1045.
57. Harding, C.,Heuser, J. and Stahl, P. (1983). Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes. J. Cell Biol. 97, 329-339.
58. Harding, C.,Heuser, J. and 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.
59. Henne, W. M.,Buchkovich, N. J. and Emr, S. D. (2011). The ESCRT pathway. Dev. Cell 21, 77-91.
60. Henne, W. M.,Stenmark, H. and Emr, S. D. (2013). Molecular mechanisms of the membrane sculpting ESCRT pathway. Cold Spring Harb. Perspect. Biol. 5, a016766.
61. Hirano, S.,Kawasaki, M.,Ura, H.,Kato, R.,Raiborg, C.,Stenmark, H. and Wakatsuki, S. (2006). Double-sided ubiquitin binding of Hrs-UIM in endosomal protein sorting. Nat. Struct. Mol. Biol. 13, 272-277.
62. Hoshino, A.,Costa-Silva, B.,Shen, T.-L.,Rodrigues, G.,Hashimoto, A.,Tesic Mark, M.,Molina, H.,Kohsaka, S.,Di Giannatale, A.,Ceder, S. et al. (2015). Tumour exosome integrins determine organotropic metastasis. Nature 527, 329-335.
63. Hsiung, F.,Ramirez-Weber, F.-A.,Iwaki, D. D. and Kornberg, T. B. (2005). Dependence of Drosophila wing imaginal disc cytonemes on Decapentaplegic. Nature 437, 560-563.
64. Hsu, C.,Morohashi, Y.,Yoshimura, S.-I.,Manrique-Hoyos, N.,Jung, S.,Lauterbach, M. A.,Bakhti, M.,Grønborg, M.,Möbius, W.,Rhee, J. et al. (2010). Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C. J. Cell Biol. 189, 223-232.
65. Huang, H. and Kornberg, T. B. (2015). Myoblast cytonemes mediate Wg signaling from the wing imaginal disc and Delta-Notch signaling to the air sac primordium. Elife 4, e06114.
66. Hurley, J. H. (2008). ESCRT complexes and the biogenesis of multivesicular bodies. Curr. Opin. Cell Biol. 20, 4-11.
67. Hurley, J. H. (2010). The ESCRT complexes. Crit. Rev. Biochem. Mol. Biol. 45, 463-487.
68. Hurley, J. H. and Hanson, P. I. (2010). Membrane budding and scission by the ESCRT machinery: it’s all in the neck. Nat. Rev. Mol. Cell Biol. 11, 556-566.
69. Iero, M.,Valenti, R.,Huber, V.,Filipazzi, P.,Parmiani, G.,Fais, S. and Rivoltini, L. (2008). Tumour-released exosomes and their implications in cancer immunity. Cell Death Differ 15, 80-88.
70. Itoh, T. and Fukuda, M. (2006). Identification of EPI64 as a GTPase-activating protein specific for Rab27A. J. Biol. Chem. 281, 31823-31831.
71. Jahn, R. and Scheller, R. H. (2006). SNAREs–engines for membrane fusion. Nat. Rev. Mol. Cell Biol. 7, 631-643.
72. Johnstone, R. M.,Adam, M.,Hammond, J. R.,Orr, L. and Turbide, C. (1987). Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes). J. Biol. Chem. 262, 9412-9420.
73. Kalra, H.,Simpson, R. J.,Ji, H.,Aikawa, E.,Altevogt, P.,Askenase, P.,Bond, V. C.,Borràs, F. E.,Breakefield, X.,Budnik, V. et al. (2012). Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation. PLoS Biol. 10, e1001450.
74. Koles, K.,Nunnari, J.,Korkut, C.,Barria, R.,Brewer, C.,Li, Y.,Leszyk, J.,Zhang, B. and Budnik, V. (2012). Mechanism of evenness interrupted (Evi)-exosome release at synaptic boutons. J. Biol. Chem. 287, 16820-16834.
75. Korkut, C.,Ataman, B.,Ramachandran, P.,Ashley, J.,Barria, R.,Gherbesi, N. and Budnik, V. (2009). Trans-synaptic transmission of vesicular Wnt signals through Evi/Wntless. Cell 139, 393-404.
76. Lai, C. P.-K. and Breakefield, X. O. (2012). Role of exosomes/microvesicles in the nervous system and use in emerging therapies. Front. Physiol. 3, 228.
77. Latysheva, N.,Muratov, G.,Rajesh, S.,Padgett, M.,Hotchin, N. A.,Overduin, M. and Berditchevski, F. (2006). Syntenin-1 is a new component of tetraspaninenriched microdomains: mechanisms and consequences of the interaction of syntenin-1 with CD63. Mol. Cell. Biol. 26, 7707-7718.
78. Lee, J. D. and Treisman, J. E. (2001). Sightless has homology to transmembrane acyltransferases and is required to generate active Hedgehog protein. Curr. Biol. 11, 1147-1152.
79. Lee, J. J.,Ekker, S. C.,von Kessler, D. P.,Porter, J. A.,Sun, B. I. and Beachy, P. A. (1994). Autoproteolysis in hedgehog protein biogenesis. Science 266, 1528-1537.
80. Lewis, P. M.,Dunn, M. P.,McMahon, J. A.,Logan, M.,Martin, J. F.,St-Jacques, B. and McMahon, A. P. (2001). Cholesterol modification of sonic hedgehog is required for long-range signaling activity and effective modulation of signaling by Ptc1. Cell 105, 599-612.
81. Li, Y.,Zhang, H.,Litingtung, Y. and Chiang, C. (2006). Cholesterol modification restricts the spread of Shh gradient in the limb bud. Proc. Natl. Acad. Sci. USA 103, 6548-6553.
82. Liegeois, S.,Benedetto, A.,Garnier, J.-M.,Schwab, Y. and Labouesse, M. (2006). The V0-ATPase mediates apical secretion of exosomes containing Hedgehog-related proteins in Caenorhabditis elegans. J. Cell Biol. 173, 949-961.
83. Luga, V.,Zhang, L.,Viloria-Petit, A. M.,Ogunjimi, A. A.,Inanlou, M. R.,Chiu, E.,Buchanan, M.,Hosein, A. N.,Basik, M. and Wrana, J. L. (2012). Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell 151, 1542-1556.
84. Luzio, J. P.,Poupon, V.,Lindsay, M. R.,Mullock, B. M.,Piper, R. C. and Pryor, P. R. (2003). Membrane dynamics and the biogenesis of lysosomes. Mol. Membr. Biol. 20, 141-154.
85. Matusek, T.,Wendler, F.,Poles, S.,Pizette, S.,D’Angelo, G.,Furthauer, M. and Therond, P. P. (2014). The ESCRT machinery regulates the secretion and longrange activity of Hedgehog. Nature 516, 99-103.
86. Melo, S. A.,Luecke, L. B.,Kahlert, C.,Fernandez, A. F.,Gammon, S. T.,Kaye, J.,LeBleu, V. S.,Mittendorf, E. A.,Weitz, J.,Rahbari, N. et al. (2015). Glypican-1 identifies cancer exosomes and detects early pancreatic cancer. Nature 523, 177-182.
87. Micchelli, C. A.,The, I.,Selva, E.,Mogila, V. and Perrimon, N. (2002). Rasp, a putative transmembrane acyltransferase, is required for Hedgehog signaling. Development 129, 843-851.
88. Mills, I. G.,Jones, A. T. and Clague, M. J. (1998). Involvement of the endosomal autoantigen EEA1 in homotypic fusion of early endosomes. Curr. Biol. 8, 881-884.
89. Misra, S. and Hurley, J. H. (1999). Crystal structure of a phosphatidy linositol 3-phosphate-specific membrane-targeting motif, the FYVE domain of Vps27p. Cell 97, 657-666.
90. Mobius, W.,Ohno-Iwashita, Y.,van Donselaar, E. G.,Oorschot, V. M. J.,Shimada, Y.,Fujimoto, T.,Heijnen, H. F. G.,Geuze, H. J. and Slot, J.W. (2002). Immunoelectron microscopic localization of cholesterol using biotinylated and non-cytolytic perfringolysin O. J. Histochem. Cytochem. 50, 43-55.
91. Montecalvo, A.,Larregina, A. T.,Shufesky, W. J.,Stolz, D. B.,Sullivan, M. L. G.,Karlsson, J. M.,Baty, C. J.,Gibson, G. A.,Erdos, G.,Wang, Z. et al. (2012). Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood 119, 756-766.
92. Mulligan, K. A.,Fuerer, C.,Ching, W.,Fish, M.,Willert, K. and Nusse, R. (2012). Secreted Wingless-interacting molecule (Swim) promotes long-range signaling by maintaining Wingless solubility. Proc. Natl. Acad. Sci. USA 109, 370-377.
93. Muralidharan-Chari, V.,Clancy, J. W.,Sedgwick, A. and D’Souza-Schorey, C. (2010). Microvesicles: mediators of extracellular communication during cancer progression. J. Cell Sci. 123, 1603-1611.
94. Nabhan, J. F.,Hu, R.,Oh, R. S.,Cohen, S. N. and Lu, Q. (2012). Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 protein. Proc. Natl. Acad. Sci. USA 109, 4146-4151.
95. Niehrs, C. (2010). On growth and form: a Cartesian coordinate system of Wnt and BMP signaling specifies bilaterian body axes. Development 137, 845-857.
96. Ogawa, Y.,Miura, Y.,Harazono, A.,Kanai-Azuma, M.,Akimoto, Y.,Kawakami, H.,Yamaguchi, T.,Toda, T.,Endo, T.,Tsubuki, M. et al. (2011). Proteomic analysis of two types of exosomes in human whole saliva. Biol. Pharm. Bull. 34, 13-23.
97. Ostrowski, M.,Carmo, N. B.,Krumeich, S.,Fanget, I.,Raposo, G.,Savina, A.,Moita, C. F.,Schauer, K.,Hume, A. N.,Freitas, R. P. et al. (2010). Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat. Cell Biol. 12, 19-30; sup pp 11-13.
98. Pan, B. T.,Teng, K.,Wu, C.,Adam, M. and 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.
99. Panakova, D.,Sprong, H.,Marois, E.,Thiele, C. and Eaton, S. (2005). Lipoprotein particles are required for Hedgehog and Wingless signalling. Nature 435, 58-65.
100. Parchure, A.,Vyas, N.,Ferguson, C.,Parton, R. G. and Mayor, S. (2015). Oligomerization and endocytosis of Hedgehog is necessary for its efficient exovesicular secretion. Mol. Biol. Cell 26, 4700-4717.
101. Peinado, H.,Aleckovic, M.,Lavotshkin, S.,Matei, I.,Costa-Silva, B.,Moreno-Bueno, G.,Hergueta-Redondo, M.,Williams, C.,Garcia-Santos, G.,Ghajar, C. M. et al. (2012). Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET. Nat. Med. 18, 883-891.
102. Perrimon, N. (1994). The genetic basis of patterned baldness in Drosophila. Cell 76, 781-784.
103. Perrimon, N.,Pitsouli, C. and Shilo, B.-Z. (2012). Signaling mechanisms controlling cell fate and embryonic patterning. Cold Spring Harb. Perspect. Biol. 4, a005975.
104. Piper, R. C. and Luzio, J. P. (2007). Ubiquitin-dependent sorting of integral membrane proteins for degradation in lysosomes. Curr. Opin. Cell Biol. 19, 459-465.
105. Pols, M. S. and Klumperman, J. (2009). Trafficking and function of the tetraspanin CD63. Exp. Cell Res. 315, 1584-1592.
106. Porter, J. A.,von Kessler, D. P.,Ekker, S. C.,Young, K. E.,Lee, J. J.,Moses, K. and Beachy, P. A. (1995). The product of hedgehog autoproteolytic cleavage active in local and long-range signalling. Nature 374, 363-366.
107. Proux-Gillardeaux, V.,Raposo, G.,Irinopoulou, T. and Galli, T. (2007). Expression of the Longin domain of TI-VAMP impairs lysosomal secretion and epithelial cell migration. Biol. Cell 99, 261-271.
108. Raiborg, C. and Stenmark, H. (2009). The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature 458, 445-452.
109. Raiborg, C.,Bache, K. G.,Mehlum, A.,Stang, E. and Stenmark, H. (2001a). Hrs recruits clathrin to early endosomes. EMBO J. 20, 5008-5021.
110. Raiborg, C.,Bremnes, B.,Mehlum, A.,Gillooly, D. J.,D’Arrigo, A.,Stang, E. and Stenmark, H. (2001b). FYVE and coiled-coil domains determine the specific localisation of Hrs to early endosomes. J. Cell Sci. 114, 2255-2263.
111. Raiborg, C.,Bache, K. G.,Gillooly, D. J.,Madshus, I. H.,Stang, E. and Stenmark, H. (2002). Hrs sorts ubiquitinated proteins into clathrin-coated microdomains of early endosomes. Nat. Cell Biol. 4, 394-398.
112. Raiborg, C.,Wesche, J.,Malerod, L. and Stenmark, H. (2006). Flat clathrin coats on endosomes mediate degradative protein sorting by scaffolding Hrs in dynamic microdomains. J. Cell Sci. 119, 2414-2424.
113. Rajendran, L.,Honsho, M.,Zahn, T. R.,Keller, P.,Geiger, K. D.,Verkade, P. and Simons, K. (2006). Alzheimer’s disease beta-amyloid peptides are released in association with exosomes. Proc. Natl. Acad. Sci. USA 103, 11172-11177.
114. Rak, J. (2015). Cancer: organ-seeking vesicles. Nature 527, 312-314.
115. Ramirez-Weber, F.-A. and Kornberg, T. B. (1999). Cytonemes: cellular processes that project to the principal signaling center in Drosophila imaginal discs. Cell 97, 599-607.
116. Ren, X. and Hurley, J. H. (2010). VHS domains of ESCRT-0 cooperate in highavidity binding to polyubiquitinated cargo. EMBO J. 29, 1045-1054.
117. Robbins, P. D. and Morelli, A. E. (2014). Regulation of immune responses by extracellular vesicles. Nat. Rev. Immunol. 14, 195-208.
118. Sabin, K. and Kikyo, N. (2014). Microvesicles as mediators of tissue regeneration. Transl. Res. 163, 286-295.
119. Sanchez-Hernandez, D.,Sierra, J.,Ortigao-Farias, J. R. and Guerrero, I. (2012). The WIF domain of the human and Drosophila Wif-1 secreted factors confers specificity for Wnt or Hedgehog. Development 139, 3849-3858.
120. 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.
121. Schorey, J. S.,Cheng, Y.,Singh, P. P. and Smith, V. L. (2015). Exosomes and other extracellular vesicles in host-pathogen interactions. EMBO Rep. 16, 24-43.
122. Serralbo, O. and Marcelle, C. (2014). Migrating cells mediate long-range WNT signaling. Development 141, 2057-2063.
123. Sheldon, H.,Heikamp, E.,Turley, H.,Dragovic, R.,Thomas, P.,Oon, C. E.,Leek, R.,Edelmann, M.,Kessler, B.,Sainson, R. C. A. et al. (2010). New mechanism for Notch signaling to endothelium at a distance by Delta-like 4 incorporation into exosomes. Blood 116, 2385-2394.
124. Shen, B.,Wu, N.,Yang, J.-M. and Gould, S. J. (2011). Protein targeting to exosomes/microvesicles by plasma membrane anchors. J. Biol. Chem. 286, 14383-14395.
125. Silverman, J. M.,Fernando, S. M.,Grad, L. I.,Hill, A. F.,Turner, B. J.,Yerbury, J. J. and Cashman, N. R. (2016). Disease mechanisms in ALS: misfolded SOD1 transferred through exosome-dependent and exosome-independent pathways. Cell. Mol. Neurobiol. 36, 377-381.
126. Soto, C. (2003). Unfolding the role of protein misfolding in neurodegenerative diseases. Nat. Rev. Neurosci. 4, 49-60.
127. Stahelin, R. V.,Long, F.,Diraviyam, K.,Bruzik, K. S.,Murray, D. and Cho, W. (2002). Phosphatidylinositol 3-phosphate induces the membrane penetration of the FYVE domains of Vps27p and Hrs. J. Biol. Chem. 277, 26379-26388.
128. Stanganello, E. and Scholpp, S. (2016). Role of cytonemes in Wnt transport. J. Cell Sci. 129, 665-672.
129. Stanganello, E.,Hagemann, A. I. H.,Mattes, B.,Sinner, C.,Meyen, D.,Weber, S.,Schug, A.,Raz, E. and Scholpp, S. (2015). Filopodia-based Wnt transport during vertebrate tissue patterning. Nat. Commun. 6, 5846.
130. Strigini, M. and Cohen, S. M. (1997). A Hedgehog activity gradient contributes to AP axial patterning of the Drosophila wing. Development 124, 4697-4705.
131. Stuffers, S.,Sem Wegner, C.,Stenmark, H. and Brech, A. (2009). Multivesicular endosome biogenesis in the absence of ESCRTs. Traffic 10, 925-937.
132. Tanaka, Y.,Okada, Y. and Hirokawa, N. (2005). FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left-right determination. Nature 435, 172-177.
133. Tang, S.,Henne, W. M.,Borbat, P. P.,Buchkovich, N. J.,Freed, J. H.,Mao, Y.,Fromme, J. C. and Emr, S. D. (2015). Structural basis for activation, assembly and membrane binding of ESCRT-III Snf7 filaments. Elife 4, e12548.
134. Thery, C. (2015). Cancer: diagnosis by extracellular vesicles. Nature 523, 161-162.
135. Thery, C.,Boussac, M.,Veron, 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.
136. Thery, C.,Duban, L.,Segura, E.,Veron, P.,Lantz, O. and Amigorena, S. (2002). Indirect activation of naïve CD4+ T cells by dendritic cell-derived exosomes. Nat. Immunol. 3, 1156-1162.
137. Tian, T.,Zhu, Y.-L.,Zhou, Y.-Y.,Liang, G.-F.,Wang, Y.-Y.,Hu, F.-H. and Xiao, Z.-D. (2014). Exosome uptake through clathrin-mediated endocytosis and macropinocytosis and mediating miR-21 delivery. J. Biol. Chem. 289, 22258-22267.
138. Trajkovic, K.,Hsu, C.,Chiantia, S.,Rajendran, L.,Wenzel, D.,Wieland, F.,Schwille, P.,Brugger, B. and Simons, M. (2008). Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319, 1244-1247.
139. van Amerongen, R. and Nusse, R. (2009). Towards an integrated view of Wnt signaling in development. Development 136, 3205-3214.
140. van Niel, G.,Charrin, S.,Simoes, S.,Romao, M.,Rochin, L.,Saftig, P.,Marks, M. S.,Rubinstein, E. and Raposo, G. (2011). The tetraspanin CD63 regulates ESCRT-independent and -dependent endosomal sorting during melanogenesis. Dev. Cell 21, 708-721.
141. Vyas, N.,Walvekar, A.,Tate, D.,Lakshmanan, V.,Bansal, D.,Lo Cicero, A.,Raposo, G.,Palakodeti, D. and Dhawan, J. (2014). Vertebrate Hedgehog is secreted on two types of extracellular vesicles with different signaling properties. Sci. Rep. 4, 7357.
142. Wehman, A. M.,Poggioli, C.,Schweinsberg, P.,Grant, B. D. and Nance, J. (2011). The P4-ATPase TAT-5 inhibits the budding of extracellular vesicles in C. elegans embryos. Curr. Biol. 21, 1951-1959.
143. Wollert, T.,Wunder, C.,Lippincott-Schwartz, J. and Hurley, J. H. (2009). Membrane scission by the ESCRT-III complex. Nature 458, 172-177.
144. Wubbolts, R.,Leckie, R. S.,Veenhuizen, P. T. M.,Schwarzmann, G.,Mobius, W.,Hoernschemeyer, J.,Slot, J.-W.,Geuze, H. J. and Stoorvogel, W. (2003). Proteomic and biochemical analyses of human B cell-derived exosomes: potential implications for their function and multivesicular body formation. J. Biol. Chem. 278, 10963-10972.
145. Yamazaki, Y.,Palmer, L.,Alexandre, C.,Kakugawa, S.,Beckett, K.,Gaugue, I.,Palmer, R. H. and Vincent, J.-P. (2016). Godzilla-dependent transcytosis promotesWingless signalling in Drosophila wing imaginal discs. Nat. Cell Biol. 18, 451-457.
146. Yang, J.-M. and Gould, S. J. (2013). The cis-acting signals that target proteins to exosomes and microvesicles. Biochem. Soc. Trans. 41, 277-282.
147. Zecca, M.,Basler, K. and Struhl, G. (1996). Direct and long-range action of a wingless morphogen gradient. Cell 87, 833-844.
148. Zeng, X.,Goetz, J. A.,Suber, L. M.,Scott, W. J.,Jr, Schreiner, C. M. and Robbins, D. J. (2001). A freely diffusible form of Sonic hedgehog mediates longrange signalling. Nature 411, 716-720.
149. Zhang, T. and Hong, W. (2001). Ykt6 forms a SNARE complex with syntaxin 5, GS28, and Bet1 and participates in a late stage in endoplasmic reticulum-Golgi transport. J. Biol. Chem. 276, 27480-27487.
150. Zhang, L.,Zhang, S.,Yao, J.,Lowery, F. J.,Zhang, Q.,Huang, W.-C.,Li, P.,Li, M.,Wang, X.,Zhang, C. et al. (2015). Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth. Nature 527, 100-104.
151. Zhu, W.,Huang, L.,Li, Y.,Zhang, X.,Gu, J.,Yan, Y.,Xu, X.,Wang, M.,Qian, H. and Xu, W. (2012). Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo. Cancer Lett. 315, 28-37.