Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake
Tóm tắt
Extracellular vesicles are a heterogeneous group of membrane-limited vesicles loaded with various proteins, lipids, and nucleic acids. Release of extracellular vesicles from its cell of origin occurs either through the outward budding of the plasma membrane or through the inward budding of the endosomal membrane, resulting in the formation of multivesicular bodies, which release vesicles upon fusion with the plasma membrane. The release of vesicles can facilitate intercellular communication by contact with or by internalization of contents, either by fusion with the plasma membrane or by endocytosis into “recipient” cells. Although the interest in extracellular vesicle research is increasing, there are still no real standards in place to separate or classify the different types of vesicles. This review provides an introduction into this expanding and complex field of research focusing on the biogenesis, nucleic acid cargo loading, content, release, and uptake of extracellular vesicles.
Tài liệu tham khảo
Abrami L, Brandi L, Moayeri M et al (2013) Hijacking multivesicular bodies enables long-term and exosome-mediated long-distance action of anthrax toxin. Cell Rep 5:986–996. doi:10.1016/j.celrep.2013.10.019
Akers JC, Gonda D, Kim R et al (2013) Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J Neurooncol 113:1–11
Al-Nedawi K, Meehan B, Micallef J et al (2008) Intercellular transfer of the oncogenic receptor EGFRvIII by microvesicles derived from tumour cells. Nat Cell Biol 10:619–624. doi:10.1038/ncb1725
Alonso R, Mazzeo C, Mérida I, Izquierdo M (2007) A new role of diacylglycerol kinase α on the secretion of lethal exosomes bearing Fas ligand during activation-induced cell death of T lymphocytes. Biochimie 89:213–221. doi:10.1016/j.biochi.2006.07.018
Alonso R, Mazzeo C, Rodriguez MC et al (2011) Diacylglycerol kinase α regulates the formation and polarisation of mature multivesicular bodies involved in the secretion of Fas ligand-containing exosomes in T lymphocytes. Cell Death Differ 18:1161–1173. doi:10.1038/cdd.2010.184
Arroyo JD, Chevillet JR, Kroh EM et al (2011) Argonaute2 complexes carry a population of circulating microRNAs independent of vesicles in human plasma. Proc Natl Acad Sci U S A 108:5003–5008. doi:10.1073/pnas.1019055108
Atai NA, Balaj L, Van Veen H et al (2013) Heparin blocks transfer of extracellular vesicles between donor and recipient cells. J Neurooncol 115:343–351. doi:10.1007/s11060-013-1235-y
Babst M, Katzmann DJ, Estepa-Sabal EJ et al (2002) ESCRT-III: an endosome-associated heterooligomeric protein complex required for MVB sorting. Dev Cell 3:271–282. doi:10.1016/S1534-5807(02)00220-4
Bache KG, Brech A, Mehlum A, Stenmark H (2003) Hrs regulates multivesicular body formation via ESCRT recruitment to endosomes. J Cell Biol 162:435–442. doi:10.1083/jcb.200302131
Baietti MF, Zhang Z, Mortier E et al (2012) Syndecan–syntenin–ALIX regulates the biogenesis of exosomes. Nat Cell Biol 14:677–685
Baj-Krzyworzeka M, Szatanek R, Wȩglarczyk K et al (2006) Tumour-derived microvesicles carry several surface determinants and mRNA of tumour cells and transfer some of these determinants to monocytes. Cancer Immunol Immunother 55:808–818. doi:10.1007/s00262-005-0075-9
Balaj L, Lessard R, Dai L et al (2011) Tumour microvesicles contain retrotransposon elements and amplified oncogene sequences. Nat Commun 2:180. doi:10.1038/ncomms1180
Barrès C, Blanc L, Bette-Bobillo P et al (2010) Galectin-5 is bound onto the surface of rat reticulocyte exosomes and modulates vesicle uptake by macrophages. Blood 115:696–705. doi:10.1182/blood-2009-07-231449
Barteneva NS, Maltsev N, Vorobjev IA (2013) Microvesicles and intercellular communication in the context of parasitism. Front Cell Infect Microbiol 3:49. doi:10.3389/fcimb.2013.00049
Batagov AO, Kurochkin IV (2013) Exosomes secreted by human cells transport largely mRNA fragments that are enriched in the 3′-untranslated regions. Biol Direct. doi:10.1186/1745-6150-8-12
Beckler M, Higginbotham JN, Franklin JL et al (2013) Proteomic analysis of exosomes from mutant KRAS colon cancer cells identifies intercellular transfer of mutant KRAS. Mol Cell Proteomics 12:343–355. doi:10.1074/mcp.M112.022806
Benedetto A, Liegeois S, Garnier J-M, et al (2006) A novel exosome-mediated apical secretion pathway involving the V0-sector of the V-ATPase in C. elegans epidermal cells. Eur Worm Meet
Bicalho B, Holovati JL, Acker JP (2013) Phospholipidomics reveals differences in glycerophosphoserine profiles of hypothermically stored red blood cells and microvesicles. Biochim Biophys Acta 1828:317–326. doi:10.1016/j.bbamem.2012.10.026
Bishop N, Woodman P (2001) TSG101/mammalian VPS23 and mammalian VPS28 interact directly and are recruited to VPS4-induced endosomes. J Biol Chem 276:11735–11742. doi:10.1074/jbc.M009863200
Bolukbasi MF, Mizrak A, Ozdener GB et al (2012) miR-1289 and “Zipcode”-like sequence enrich mrnas in microvesicles. Mol Ther 1:e10
Brouwers JF, Aalberts M, Jansen JWA et al (2013) Distinct lipid compositions of two types of human prostasomes. Proteomics 13:1660–1666. doi:10.1002/pmic.201200348
Bucki R, Bachelot-Loza C, Zachowski A et al (1998) Calcium induces phospholipid redistribution and microvesicle release in human erythrocyte membranes by independent pathways. Biochemistry 37:15383–15391. doi:10.1021/bi9805238
Carayon K, Chaoui K, Ronzier E et al (2011) Proteolipidic composition of exosomes changes during reticulocyte maturation. J Biol Chem 286:34426–34439. doi:10.1074/jbc.M111.257444
Cheng L, Sun X, Scicluna BJ et al (2013) Characterization and deep sequencing analysis of exosomal and non-exosomal miRNA in human urine. Kidney Int. doi:10.1038/ki.2013.502
Christianson HC, Svensson KJ, van Kuppevelt TH et al (2013) Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity. Proc Natl Acad Sci USA 110:17380–17385. doi:10.1073/pnas.1304266110
Cocucci E, Racchetti G, Meldolesi J (2009) Shedding microvesicles: artefacts no more. Trends Cell Biol 19:43–51
Colombo M, Moita C, van Niel G et al (2013) Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J Cell Sci 126:5553–5565. doi:10.1242/jcs.128868
Conde-Vancells J, Rodriguez-Suarez E, Embade N et al (2008) Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J Proteome Res 7:5157–5166. doi:10.1021/pr8004887
Cossetti C, Iraci N, Mercer TR et al (2014) Extracellular vesicles from neural stem cells transfer IFN-γ via Ifngr1 to activate Stat1 signaling in target cells. Mol Cell 56:193–204. doi:10.1016/j.molcel.2014.08.020
Crescitelli R, Lässer C, Szabó TG et al (2013) Distinct RNA profiles in subpopulations of extracellular vesicles: apoptotic bodies, microvesicles and exosomes. J Extracell vesicles 2:1–10. doi:10.3402/jev.v2i0.20677
de Jong OG, Verhaar MC, Chen Y, et al (2012) Cellular stress conditions are reflected in the protein and RNA content of endothelial cell-derived exosomes. J Extracell Vesicles
Denzer K, Kleijmeer MJ, Heijnen HF et al (2000) Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci 113(Pt 19):3365–3374
Fader CM, Sánchez DG, Mestre MB, Colombo MI (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. doi:10.1016/j.bbamcr.2009.09.011
Feng D, Zhao WL, Ye YY et al (2010) Cellular internalization of exosomes occurs through phagocytosis. Traffic 11:675–687. doi:10.1111/j.1600-0854.2010.01041.x
Fernandez-Borja M, Wubbolts R, Calafat J et al (1999) Multivesicular body morphogenesis requires phosphatidylinositol 3-kinase activity. Curr Biol 9:55–58. doi:10.1016/S0960-9822(99)80048-7
Fitzner D, Schnaars M, van Rossum D et al (2011) Selective transfer of exosomes from oligodendrocytes to microglia by macropinocytosis. J Cell Sci 124:447–458. doi:10.1242/jcs.074088
Frühbeis C, Fröhlich D, Krämer-Albers EM (2012) Emerging roles of exosomes in neuron-glia communication. Front Physiol. doi:10.3389/fphys.2012.00119
Frühbeis C, Fröhlich D, Kuo WP et al (2013) Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication. PLoS Biol. doi:10.1371/journal.pbio.1001604
Ghossoub R, Lembo F, Rubio A et al (2014) Syntenin-ALIX exosome biogenesis and budding into multivesicular bodies are controlled by ARF6 and PLD2. Nat Commun 5:3477. doi:10.1038/ncomms4477
Gibbings DJ, Ciaudo C, Erhardt M, Voinnet O (2009) Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nat Cell Biol 11:1143–1149
Gonzalez-Begne M, Lu B, Han X et al (2009) Proteomic analysis of human parotid gland exosomes by multidimensional protein identification technology (MudPIT). J Proteome Res 8:1304–1314
Gould SJ, Raposo G (2013) As we wait: coping with an imperfect nomenclature for extracellular vesicles. J Extracell Vesicles 2:3–5. doi:10.3402/jev.v2i0.20389
Gould SJ, Booth AM, Hildreth JEK (2003) The Trojan exosome hypothesis. Proc Natl Acad Sci USA 100:10592–10597. doi:10.1073/pnas.1831413100
Graner MW, Alzate O, Dechkovskaia AM et al (2009) Proteomic and immunologic analyses of brain tumor exosomes. FASEB J 23:1541–1557. doi:10.1096/fj.08-122184
Grant BD, Donaldson JG (2009) Pathways and mechanisms of endocytic recycling. Nat Rev Mol Cell Biol 10:597–608. doi:10.1038/nrm2755
Guduric-Fuchs J, O’Connor A, Camp B et al (2012) Selective extracellular vesicle-mediated export of an overlapping set of microRNAs from multiple cell types. BMC Genom 13:357. doi:10.1186/1471-2164-13-357
Guescini M, Genedani S, Stocchi V, Agnati LF (2010) Astrocytes and Glioblastoma cells release exosomes carrying mtDNA. J Neural Transm 117:1–4. doi:10.1007/s00702-009-0288-8
György B, Szabó TG, Pásztói M et al (2011) Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles. Cell Mol Life Sci 68:2667–2688
Henderson MC, Azorsa DO (2012) The genomic and proteomic content of cancer cell-derived exosomes. Front Oncol 2:3389
Henne WM, Buchkovich NJ, Emr SD (2011) The ESCRT pathway. Dev Cell 21:77–91
Henne WM, Stenmark H, Emr SD (2013) Molecular mechanisms of the membrane sculpting ESCRT pathway. Cold Spring Harb Perspect Med. doi:10.1101/cshperspect.a016766
Hsu C, Morohashi Y, Yoshimura SI et al (2010) Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C. J Cell Biol 189:223–232. doi:10.1083/jcb.200911018
Huang X, Yuan T, Tschannen M et al (2013) Characterization of human plasma-derived exosomal RNAs by deep sequencing. BMC Genom 14:319. doi:10.1186/1471-2164-14-319
Jenjaroenpun P, Kremenska Y, Nair VM et al (2013) Characterization of RNA in exosomes secreted by human breast cancer cell lines using next-generation sequencing. PeerJ 1:e201. doi:10.7717/peerj.201
Kalra H, Simpson RJ, Ji H et al (2012) Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation. PLoS Biol. doi:10.1371/journal.pbio.1001450
Katzmann DJ, Babst M, Emr SD (2001) Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell 106:145–155. doi:10.1016/S0092-8674(01)00434-2
Kim D-K, Kang B, Kim OY et al (2013) EVpedia: an integrated database of high-throughput data for systemic analyses of extracellular vesicles. J Extracell Vesicles 2:1–7. doi:10.3402/jev.v2i0.20384
Koppers-Lalic D, Hackenberg M, Bijnsdorp IV et al (2014) Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes. Cell Reports 8:1649–1658
Kosaka N, Iguchi H, Yoshioka Y et al (2010) Secretory mechanisms and intercellular transfer of microRNAs in living cells. J Biol Chem 285:17442–17452. doi:10.1074/jbc.M110.107821
Lai CP, Kim EY, Badr CE et al (2015) Visualization and tracking of tumour extracellular vesicle delivery and RNA translation using multiplexed reporters. Nat Commun 6:7029. doi:10.1038/ncomms8029
Laulagnier K, Grand D, Dujardin A et al (2004) PLD2 is enriched on exosomes and its activity is correlated to the release of exosomes. FEBS Lett 572:11–14. doi:10.1016/j.febslet.2004.06.082
Li L, Zhu D, Huang L et al (2012) Argonaute 2 complexes selectively protect the circulating micrornas in cell-secreted microvesicles. PLoS One. doi:10.1371/journal.pone.0046957
Li CCY, Eaton SA, Young PE et al (2013) Glioma microvesicles carry selectively packaged coding and noncoding RNAs which alter gene expression in recipient cells. RNA Biol 10:1333–1344. doi:10.4161/rna.25281
Li Y, Zheng Q, Bao C et al (2015) Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res. doi:10.1038/cr.2015.82
Llorente A, Skotland T, Sylvänne T et al (2013) Molecular lipidomics of exosomes released by PC-3 prostate cancer cells. Biochim Biophys Acta 1831:1302–1309. doi:10.1016/j.bbalip.2013.04.011
Logan MR, Lacy P, Odemuyiwa SO et al (2006) A critical role for vesicle-associated membrane protein-7 in exocytosis from human eosinophils and neutrophils. Allergy Eur J Allergy Clin Immunol 61:777–784. doi:10.1111/j.1398-9995.2006.01089.x
Lötvall J, Hill AF, Hochberg F et al (2014) Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles. J Extracell Vesicles 3:26913. doi:10.3402/jev.v3.26913
Luga V, Zhang L, Viloria-Petit AM et al (2012) Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. Cell 151:1542–1556. doi:10.1016/j.cell.2012.11.024
Marcilla A, Trelis M, Cortés A et al (2012) Extracellular vesicles from parasitic helminths contain specific excretory/secretory proteins and are internalized in intestinal host cells. PLoS One. doi:10.1371/journal.pone.0045974
Mathivanan S, Simpson RJ (2009) ExoCarta: a compendium of exosomal proteins and RNA. Proteomics 9:4997–5000. doi:10.1002/pmic.200900351
Mathivanan S, Fahner CJ, Reid GE, Simpson RJ (2012) ExoCarta 2012: database of exosomal proteins RNA and lipids. Nucleic Acids Res. doi:10.1093/nar/gkr828
Matsuo H, Chevallier J, Mayran N et al (2004) Role of LBPA and Alix in multivesicular liposome formation and endosome organization. Science 303:531–534. doi:10.1126/science.1092425
McCullough J, Fisher RD, Whitby FG et al (2008) ALIX-CHMP4 interactions in the human ESCRT pathway. Proc Natl Acad Sci USA 105:7687–7691. doi:10.1073/pnas.0801567105
Minciacchi VR, Freeman MR, Di Vizio D (2015) Extracellular vesicles in cancer: exosomes, microvesicles and the emerging role of large oncosomes. Semin Cell Dev Biol 40:41–51
Momen-Heravi F, Balaj L, Alian S et al (2012) Alternative methods for characterization of extracellular vesicles. Front Physiol 3:3389
Montecalvo A, Larregina AT, Shufesky WJ et al (2012) Mechanism of transfer of functional microRNAs between mouse dendritic cells via exosomes. Blood 119:756–766. doi:10.1182/blood-2011-02-338004
Morelli AE, Larregina AT, Shufesky WJ et al (2004) Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells. Blood 104:3257–3266. doi:10.1182/blood-2004-03-0824
Mulcahy LA, Pink RC, Carter DRF (2014) Routes and mechanisms of extracellular vesicle uptake. J Extracell Vesicles 3:1–14. doi:10.3402/jev.v3.24641
Munro TP, Magee RJ, Kidd GJ et al (1999) Mutational analysis of a heterogeneous nuclear ribonucleoprotein A2 response element for RNA trafficking. J Biol Chem 274:34389–34395. doi:10.1074/jbc.274.48.34389
Muralidharan-Chari V, Clancy J, Plou C et al (2009) ARF6-regulated shedding of tumor cell-derived plasma membrane microvesicles. Curr Biol 19:1875–1885. doi:10.1016/j.cub.2009.09.059
Nabhan JF, Hu R, Oh RS et al (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
Nakase I, Futaki S (2015) Combined treatment with a pH-sensitive fusogenic peptide and cationic lipids achieves enhanced cytosolic delivery of exosomes. Sci Rep 5:10112. doi:10.1038/srep10112
Nanbo A, Kawanishi E, Yoshida R, Yoshiyama H (2013) Exosomes derived from Epstein-Barr virus-infected cells are internalized via caveola-dependent endocytosis and promote phenotypic modulation in target cells. J Virol 87:10334–10347. doi:10.1128/JVI.01310-13
Nolte’T Hoen ENM, Buermans HPJ, Waasdorp M et al (2012) Deep sequencing of RNA from immune cell-derived vesicles uncovers the selective incorporation of small non-coding RNA biotypes with potential regulatory functions. Nucleic Acids Res 40:9272–9285. doi:10.1093/nar/gks658
Ogawa Y, Taketomi Y, Murakami M et al (2013) Small RNA transcriptomes of two types of exosomes in human whole saliva determined by next generation sequencing. Biol Pharm Bull 36:66–75. doi:10.1248/bpb.b12-00607
Ostrowski M, Carmo NB, Krumeich S et al (2010) Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 12:19–30. doi:10.1038/ncb2000
Pan BT, Johnstone RM (1983) Fate of the transferrin receptor during maturation of sheep reticulocytes in vitro: selective externalization of the receptor. Cell 33(3):967–978
Parolini I, Federici C, Raggi C et al (2009) Microenvironmental pH is a key factor for exosome traffic in tumor cells. J Biol Chem 284:34211–34222. doi:10.1074/jbc.M109.041152
Pasquet JM, Dachary-Prigent J, Nurden AT (1996) Calcium influx is a determining factor of calpain activation and microparticle formation in platelets. Eur J Biochem 239:647–654
Patel B, Patel J, Cho J-H et al (2015) Exosomes mediate the acquisition of the disease phenotypes by cells with normal genome in tuberous sclerosis complex. Oncogene. doi:10.1038/onc.2015.358
Pegtel DM, Cosmopoulos K, Thorley-Lawson DA et al (2010) Functional delivery of viral miRNAs via exosomes. Proc Natl Acad Sci USA 107:6328–6333. doi:10.1073/pnas.0914843107
Pigati L, Yaddanapudi SCS, Iyengar R et al (2010) Selective release of MicroRNA species from normal and malignant mammary epithelial cells. PLoS One 5:e13515
Plebanek MP, Mutharasan RK, Volpert O et al (2015) Nanoparticle targeting and cholesterol flux through scavenger receptor type B-1 inhibits cellular exosome uptake. Sci Rep 5:15724. doi:10.1038/srep15724
Pols MS, Klumperman J (2009) Trafficking and function of the tetraspanin CD63. Exp Cell Res 315:1584–1592
Puri N, Roche PA (2008) Mast cells possess distinct secretory granule subsets whose exocytosis is regulated by different SNARE isoforms. Proc Natl Acad Sci USA 105:2580–2585. doi:10.1073/pnas.0707854105
Raiborg C, Stenmark H (2009) The ESCRT machinery in endosomal sorting of ubiquitylated membrane proteins. Nature 458:445–452. doi:10.1038/nature07961
Rao SK, Huynh C, Proux-Gillardeaux V et al (2004) Identification of SNAREs involved in synaptotagmin VII-regulated lysosomal exocytosis. J Biol Chem 279:20471–20479. doi:10.1074/jbc.M400798200
Raposo G, Stoorvogel W (2013) Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200:373–383
Ratajczak J, Miekus K, Kucia M et al (2006) Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia 20:847–856. doi:10.1038/sj.leu.2404132
Razi M, Futter CE (2006) Distinct roles for Tsg101 and Hrs in multivesicular body formation and inward vesiculation. Mol Biol Cell 17:3469–3483. doi:10.1091/mbc.E05-11-1054
Regev-Rudzki N, Wilson DW, Carvalho TG et al (2013) Cell-cell communication between malaria-infected red blood cells via exosome-like vesicles. Cell 153:1120–1133. doi:10.1016/j.cell.2013.04.029
Ridder K, Keller S, Dams M et al (2014) Extracellular vesicle-mediated transfer of genetic information between the hematopoietic system and the brain in response to inflammation. PLoS Biol 12:e1001874
Rilla K, Pasonen-Seppänen S, Deen AJ et al (2013) Hyaluronan production enhances shedding of plasma membrane-derived microvesicles. Exp Cell Res 319:2006–2018. doi:10.1016/j.yexcr.2013.05.021
Rilla K, Siiskonen H, Tammi M, Tammi R (2014) Hyaluronan-coated extracellular vesicles- A novel link between hyaluronan and cancer. Adv Cancer Res 123:121–148. doi:10.1016/B978-0-12-800092-2.00005-8
Roucourt B, Meeussen S, Bao J et al (2015) Heparanase activates the syndecan-syntenin-ALIX exosome pathway. Cell Res 25:412–428. doi:10.1038/cr.2015.29
Savina A, Furlán M, Vidal M, Colombo MI (2003) Exosome release is regulated by a calcium-dependent mechanism in K562 cells. J Biol Chem 278:20083–20090. doi:10.1074/jbc.M301642200
Servier LL (2016). http://www.servier.com/Powerpoint-image-bank
Shields SB, Oestreich AJ, Winistorfer S et al (2009) ESCRT ubiquitin-binding domains function cooperatively during MVB cargo sorting. J Cell Biol 185:213–224. doi:10.1083/jcb.200811130
Simpson RJ, Kalra H, Mathivanan S (2012) ExoCarta as a resource for exosomal research. J Extracell Vesicles. doi:10.3402/jev.v1i0.18374
Skog J, Würdinger T, van Rijn S et al (2008) Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10:1470–1476. doi:10.1038/ncb1800
Squadrito ML, Baer C, Burdet F et al (2014) Endogenous RNAs modulate MicroRNA sorting to exosomes and transfer to acceptor cells. Cell Reports 8:1432–1446
Stenmark H (2009) Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol 10:513–525. doi:10.1038/nrm2728
Stoorvogel W, Strous GJ, Geuze HJ et al (1991) Late endosomes derive from early endosomes by maturation. Cell 65:417–427. doi:10.1016/0092-8674(91)90459-C
Stuffers S, Sem Wegner C, Stenmark H, Brech A (2009) Multivesicular endosome biogenesis in the absence of ESCRTs. Traffic 10:925–937. doi:10.1111/j.1600-0854.2009.00920.x
Subra C, Laulagnier K, Perret B, Record M (2007) Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies. Biochimie 89:205–212
Svensson KJ, Christianson HC, Wittrup A et al (2013) Exosome uptake depends on ERK1/2-heat shock protein 27 signaling and lipid raft-mediated endocytosis negatively regulated by caveolin-1. J Biol Chem 288:17713–17724. doi:10.1074/jbc.M112.445403
Tamai K, Tanaka N, Nakano T et al (2010) Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein. Biochem Biophys Res Commun 399:384–390. doi:10.1016/j.bbrc.2010.07.083
Tauro BJ, Greening DW, Mathias RA et al (2012) Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes. Methods 56:293–304. doi:10.1016/j.ymeth.2012.01.002
Théry C, Boussac M, Véron P et al (2001) Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J Immunol 166:7309–7318. doi:10.4049/jimmunol.166.12.7309
Théry C, Zitvogel L, Amigorena S (2002) Exosomes: composition, biogenesis and function. Nat Rev Immunol 2:569–579. doi:10.1038/nri855
Théry C, Ostrowski M, Segura E (2009) Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 9:581–593. doi:10.1038/nri2567
Tiwari N, Wang CC, Brochetta C et al (2008) VAMP-8 segregates mast cell-preformed mediator exocytosis from cytokine trafficking pathways. Blood 111:3665–3674. doi:10.1182/blood-2007-07-103309
Turiák L, Misják P, Szabó TG et al (2011) Proteomic characterization of thymocyte-derived microvesicles and apoptotic bodies in BALB/c mice. J Proteomics 74:2025–2033. doi:10.1016/j.jprot.2011.05.023
Van Blitterswijk WJ, De Veer G, Krol JH, Emmelot P (1982) Comparative lipid analysis of purified plasma membranes and shed extracellular membrane vesicles from normal murine thymocytes and leukemic GRSL cells. Biochim Biophys Acta 688:495–504. doi:10.1016/0005-2736(82)90361-3
Vickers KC, Remaley AT (2012) Lipid-based carriers of microRNAs and intercellular communication. Curr Opin Lipidol 23:91–97
Vickers KC, Palmisano BT, Shoucri BM et al (2011) MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins. Nat Cell Biol 13:423–433. doi:10.1038/ncb2210
Villarroya-Beltri C, Gutiérrez-Vázquez C, Sánchez-Cabo F et al (2013) Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs. Nat Commun 4:2980. doi:10.1038/ncomms3980
Waldenström A, Gennebäck N, Hellman U, Ronquist G (2012) Cardiomyocyte microvesicles contain DNA/RNA and convey biological messages to target cells. PLoS One. doi:10.1371/journal.pone.0034653
Wang T, Gilkes DM, Takano N et al (2014) Hypoxia-inducible factors and RAB22A mediate formation of microvesicles that stimulate breast cancer invasion and metastasis. Proc Natl Acad Sci USA 111:E3234–E3242. doi:10.1073/pnas.1410041111
Witwer KW, Buzás EI, Bemis LT et al (2013) Standardization of sample collection, isolation and analysis methods in extracellular vesicle research. J Extracell Vesicles 2:1–25. doi:10.3402/jev.v2i0.20360
Wollert T, Hurley JH (2010) Molecular mechanism of multivesicular body biogenesis by ESCRT complexes. Nature 464:864–869. doi:10.1038/nature08849
Wubbolts R, Leckie RS, Veenhuizen PTM et al (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. doi:10.1074/jbc.M207550200
Xiao D, Ohlendorf J, Chen Y et al (2012) Identifying mRNA, microrna and protein profiles of melanoma exosomes. PLoS One. doi:10.1371/journal.pone.0046874
Yang J-M, Gould SJ (2013) The cis-acting signals that target proteins to exosomes and microvesicles. Biochem Soc Trans 41:277–282. doi:10.1042/BST20120275
Zaborowski MP, Balaj L, Breakefield XO, Lai CP (2015) Extracellular vesicles: composition, biological relevance, and methods of study. Bioscience 65:783–797. doi:10.1093/biosci/biv084
