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Cited by 2,362Extracellular vesicles in diseaseCellular transport and secretionNanoparticle-Based Drug Delivery

Current knowledge on exosome biogenesis and release

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Hessvik, Nina Pettersen, Llorente, Alicia·2018·Cellular and Molecular Life Sciences
DOI 10.1007/s00018-017-2595-9PMC PMC5756260
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Abstract

Exosomes are nanosized membrane vesicles released by fusion of an organelle of the endocytic pathway, the multivesicular body, with the plasma membrane. This process was discovered more than 30 years ago, and during these years, exosomes have gone from being considered as cellular waste disposal to mediate a novel mechanism of cell-to-cell communication. The exponential interest in exosomes experienced during recent years is due to their important roles in health and disease and to their potential clinical application in therapy and diagnosis. However, important aspects of the biology of exosomes remain unknown. To explore the use of exosomes in the clinic, it is essential that the basic molecular mechanisms behind the transport and function of these vesicles are better understood. We have here summarized what is presently known about how exosomes are formed and released by cells. Moreover, other cellular processes related to exosome biogenesis and release, such as autophagy and lysosomal exocytosis are presented. Finally, methodological aspects related to exosome release studies are discussed.

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  • Exosomes originate from the endosomal pathway and are released by fusion of multivesicular bodies (MVBs) and plasma membranes, with sizes ranging from 30 to 150 nm.

    “Exosomes originate from the endosomal pathway and are released by fusion of multivesicular bodies (MVBs) and plasma membranes, with sizes ranging from 30 to 150 nm [120, 121].”

    From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [121]

    The Introduction (page not provided) describes exosomes as vesicles released when late endosomes or MVBs fuse with the plasma membrane, and gives their diameter as less than 150 nm. It does not specify the claimed 30 nm lower bound. (LLM, conf=0.88)

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  1. [1]Wolf P The nature and significance of platelet products in human plasma Br J Haematol 1967 13 3 269 288 10.1111/j.1365-2141.1967.tb08741.x 6025241 · DOI
  2. [2]Raposo G Stoorvogel W Extracellular vesicles: exosomes, microvesicles, and friends J Cell Biol 2013 200 4 373 383 10.1083/jcb.201211138 23420871 PMC3575529 · DOI · Paper page
  3. [3]Yanez-Mo M Siljander PR Andreu Z Zavec AB Borras FE Buzas EI Buzas K Casal E Cappello F Carvalho J Colas E Cordeiro-da Silva A Fais S Falcon-Perez JM Ghobrial IM Giebel B Gimona M Graner M Gursel I Gursel M Heegaard NH Hendrix A Kierulf P Kokubun K Kosanovic M Kralj-Iglic V Kramer-Albers EM Laitinen S Lasser C Lener T Ligeti E Line A Lipps G Llorente A Lotvall J Mancek-Keber M Marcilla A Mittelbrunn M Nazarenko I Nolte-’t Hoen EN Nyman TA O’Driscoll L Olivan M Oliveira C Pallinger E Del Portillo HA Reventos J Rigau M Rohde E Sammar M Sanchez-Madrid F Santarem N Schallmoser K Ostenfeld MS Stoorvogel W Stukelj R Van der Grein SG Vasconcelos MH Wauben MH De Wever O Biological properties of extracellular vesicles and their physiological functions J Extracell Vesicles 2015 4 27066 10.3402/jev.v4.27066 25979354 PMC4433489 · DOI · Paper page
  4. [4]Harding C Heuser J Stahl P Receptor-mediated endocytosis of transferrin and recycling of the transferrin receptor in rat reticulocytes J Cell Biol 1983 97 2 329 339 10.1083/jcb.97.2.329 6309857 PMC2112509 · DOI · Paper page
  5. [5]Pan BT Teng K Wu C Adam M Johnstone RM Electron microscopic evidence for externalization of the transferrin receptor in vesicular form in sheep reticulocytes J Cell Biol 1985 101 3 942 948 10.1083/jcb.101.3.942 2993317 PMC2113705 · DOI
  6. [6]Johnstone RM Revisiting the road to the discovery of exosomes Blood Cells Mol Dis 2005 34 3 214 219 10.1016/j.bcmd.2005.03.002 15885604 · DOI
  7. [8]Colombo M Raposo G Thery C Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles Annu Rev Cell Dev Biol 2014 30 255 289 10.1146/annurev-cellbio-101512-122326 25288114 · DOI · Paper page
  8. [9]Baixauli F Lopez-Otin C Mittelbrunn M Exosomes and autophagy: coordinated mechanisms for the maintenance of cellular fitness Front Immunol 2014 5 403 10.3389/fimmu.2014.00403 25191326 PMC4138502 · DOI
  9. [10]Hessvik NP Overbye A Brech A Torgersen ML Jakobsen IS Sandvig K Llorente A PIKfyve inhibition increases exosome release and induces secretory autophagy Cell Mol Life Sci 2016 73 24 4717 4737 10.1007/s00018-016-2309-8 27438886 PMC11108566 · DOI · Paper page
  10. [11]Mathivanan S Ji H Simpson RJ Exosomes: extracellular organelles important in intercellular communication J Proteom 2010 73 10 1907 1920 10.1016/j.jprot.2010.06.006 20601276 · DOI
  11. [12]Record M Carayon K Poirot M Silvente-Poirot S Exosomes as new vesicular lipid transporters involved in cell-cell communication and various pathophysiologies Biochim Biophys Acta 2014 1841 1 108 120 10.1016/j.bbalip.2013.10.004 24140720 · DOI
  12. [13]Becker A Thakur BK Weiss JM Kim HS Peinado H Lyden D Extracellular vesicles in cancer: cell-to-cell mediators of metastasis Cancer Cell 2016 30 6 836 848 10.1016/j.ccell.2016.10.009 27960084 PMC5157696 · DOI · Paper page
  13. [14]Peinado H Aleckovic M Lavotshkin S Matei I Costa Silva B Moreno Bueno G Hergueta Redondo M Williams C Garcia-Santos G Ghajar C Nitadori Hoshino A Hoffman C Badal K Garcia B Callahan M Yuan J Martins V Skog J Kaplan R Brady M Wolchok J Chapman P Kang Y Bromberg J Lyden D Melanoma exosomes educate bone marrow progenitor cells toward a pro-metastatic phenotype through MET Nat Med 2012 18 6 883 891 10.1038/nm.2753 22635005 PMC3645291 · DOI · Paper page
  14. [15]Costa-Silva B Aiello NM Ocean AJ Singh S Zhang H Thakur BK Becker A Hoshino A Mark MT Molina H Xiang J Zhang T Theilen TM Garcia-Santos G Williams C Ararso Y Huang Y Rodrigues G Shen TL Labori KJ Lothe IM Kure EH Hernandez J Doussot A Ebbesen SH Grandgenett PM Hollingsworth MA Jain M Mallya K Batra SK Jarnagin WR Schwartz RE Matei I Peinado H Stanger BZ Bromberg J Lyden D Pancreatic cancer exosomes initiate pre-metastatic niche formation in the liver Nat Cell Biol 2015 17 6 816 826 10.1038/ncb3169 25985394 PMC5769922 · DOI · Paper page
  15. [16]Hoshino A Costa-Silva B Shen TL Rodrigues G Hashimoto A Tesic Mark M Molina H Kohsaka S Di Giannatale A Ceder S Singh S Williams C Soplop N Uryu K Pharmer L King T Bojmar L Davies AE Ararso Y Zhang T Zhang H Hernandez J Weiss JM Dumont-Cole VD Kramer K Wexler LH Narendran A Schwartz GK Healey JH Sandstrom P Labori KJ Kure EH Grandgenett PM Hollingsworth MA de Sousa M Kaur S Jain M Mallya K Batra SK Jarnagin WR Brady MS Fodstad O Muller V Pantel K Minn AJ Bissell MJ Garcia BA Kang Y Rajasekhar VK Ghajar CM Matei I Peinado H Bromberg J Lyden D Tumour exosome integrins determine organotropic metastasis Nature 2015 527 7578 329 335 10.1038/nature15756 26524530 PMC4788391 · DOI · Paper page
  16. [17]Mobius W Ohno-Iwashita Y van Donselaar EG Oorschot VM Shimada Y Fujimoto T Heijnen HF Geuze HJ Slot JW Immunoelectron microscopic localization of cholesterol using biotinylated and non-cytolytic perfringolysin O J Histochem Cytochem 2002 50 1 43 55 10.1177/002215540205000105 11748293 · DOI
  17. [18]White IJ Bailey LM Aghakhani MR Moss SE Futter CE EGF stimulates annexin 1-dependent inward vesiculation in a multivesicular endosome subpopulation EMBO J 2006 25 1 1 12 10.1038/sj.emboj.7600759 16052208 PMC1356341 · DOI
  18. [19]Kobayashi T Startchev K Whitney AJ Gruenber J Localization of lysobisphosphatidic acid-rich membrane domains in late endosomes Biol Chem 2001 382 3 483 485 10.1515/BC.2001.059 11347897 · DOI
  19. [20]Chen Q Takada R Noda C Kobayashi S Takada S Different populations of Wnt-containing vesicles are individually released from polarized epithelial cells Sci Rep 2016 6 35562 10.1038/srep35562 27765945 PMC5073244 · DOI
  20. [21]van Niel G Raposo G Candalh C Boussac M Hershberg R Cerf-Bensussan N Heyman M Intestinal epithelial cells secrete exosome-like vesicles Gastroenterology 2001 121 2 337 349 10.1053/gast.2001.26263 11487543 · DOI
  21. [22]Tauro BJ Greening DW Mathias RA Mathivanan S Ji H Simpson RJ Two distinct populations of exosomes are released from LIM1863 colon carcinoma cell-derived organoids Mol Cell Proteom 2013 12 3 587 598 10.1074/mcp.M112.021303 PMC3591653 23230278 · DOI
  22. [23]Pocsfalvi G Stanly C Vilasi A Fiume I Capasso G Turiak L Buzas EI Vekey K Mass spectrometry of extracellular vesicles Mass Spectrom Rev 2016 35 1 3 21 10.1002/mas.21457 25705034 · DOI
  23. [24]Llorente A Skotland T Sylvanne T Kauhanen D Rog T Orlowski A Vattulainen I Ekroos K Sandvig K Molecular lipidomics of exosomes released by PC-3 prostate cancer cells Biochim Biophys Acta 2013 1831 7 1302 1309 10.1016/j.bbalip.2013.04.011 24046871 · DOI
  24. [25]Greening DW Xu R Gopal SK Rai A Simpson RJ Proteomic insights into extracellular vesicle biology—defining exosomes and shed microvesicles Expert Rev Proteom 2017 14 1 69 95 10.1080/14789450.2017.1260450 27838931 · DOI
  25. [26]Kalra H Simpson R Ji H Aikawa E Altevogt P Askenase P Bond V Borras FE Breakefield X Budnik V Buzas E Camussi G Clayton A Cocucci E Falcon Perez J Gabrielsson S Gho Y Gupta D Harsha HC Hendrix A Hill A Inal J Jenster G Krämer-Albers E-M Lim S Llorente A Lötvall J Marcilla A Mincheva Nilsson L Nazarenko I Nieuwland R Nolte-’t Hoen ENM Pandey A Patel T Piper M Pluchino S Prasad TSK Rajendran L Raposo G Record M Reid G Sanchez-Madrid F Schiffelers R Siljander P Stensballe A Stoorvogel W Taylor D Thery C Valadi H van Balkom BWM Vazquez J Vidal M Wauben MHM Yanez-Mo M Zoeller M Mathivanan S Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation PLoS Biol 2012 10 12 e1001450 e1001450 10.1371/journal.pbio.1001450 23271954 PMC3525526 · DOI · Paper page
  26. [27]Kim DK Kang B Kim OY Choi DS Lee J Kim SR Go G Yoon YJ Kim JH Jang SC Park KS Choi EJ Kim KP Desiderio DM Kim YK Lotvall J Hwang D Gho YS EVpedia: an integrated database of high-throughput data for systemic analyses of extracellular vesicles J Extracell Vesicles 2013 24009897 PMC3760654
  27. [29]Huotari J Helenius A Endosome maturation EMBO J 2011 30 17 3481 3500 10.1038/emboj.2011.286 21878991 PMC3181477 · DOI
  28. [30]Henne WM Stenmark H Emr SD Molecular mechanisms of the membrane sculpting ESCRT pathway Cold Spring Harb Perspect Biol 2013 5 9 a016766 10.1101/cshperspect.a016766 24003212 PMC3753708 · DOI
  29. [31]Colombo M Moita C van Niel G Kowal J Vigneron J Benaroch P Manel N Moita LF Thery C Raposo G Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles J Cell Sci 2013 126 Pt 24 5553 5565 10.1242/jcs.128868 24105262 · DOI
  30. [32]Tamai K Tanaka N Nakano T Kakazu E Kondo Y Inoue J Shiina M Fukushima K Hoshino T Sano K Ueno Y Shimosegawa T Sugamura K Exosome secretion of dendritic cells is regulated by Hrs, an ESCRT-0 protein Biochem Biophys Res Commun 2010 399 3 384 390 10.1016/j.bbrc.2010.07.083 20673754 · DOI
  31. [33]Gross JC Chaudhary V Bartscherer K Boutros M Active Wnt proteins are secreted on exosomes Nat Cell Biol 2012 14 10 1036 1045 10.1038/ncb2574 22983114 · DOI
  32. [34]Hoshino D Kirkbride KC Costello K Clark ES Sinha S Grega-Larson N Tyska MJ Weaver AM Exosome secretion is enhanced by invadopodia and drives invasive behavior Cell Rep 2013 5 5 1159 1168 10.1016/j.celrep.2013.10.050 24290760 PMC3873329 · DOI
  33. [36]Roucourt B Meeussen S Bao J Zimmermann P David G Heparanase activates the syndecan–syntenin–ALIX exosome pathway Cell Res 2015 25 4 412 428 10.1038/cr.2015.29 25732677 PMC4387558 · DOI
  34. [37]Friand V David G Zimmermann P Syntenin and syndecan in the biogenesis of exosomes Biol Cell 2015 107 10 331 341 10.1111/boc.201500010 26032692 · DOI
  35. [38]Stuffers S Sem Wegner C Stenmark H Brech A Multivesicular endosome biogenesis in the absence of ESCRTs Traffic 2009 10 7 925 937 10.1111/j.1600-0854.2009.00920.x 19490536 · DOI
  36. [39]Escola JM Kleijmeer MJ Stoorvogel W Griffith JM Yoshie O Geuze HJ Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes J Biol Chem 1998 273 32 20121 20127 10.1074/jbc.273.32.20121 9685355 · DOI · Paper page
  37. [40]Chairoungdua A Smith DL Pochard P Hull M Caplan MJ Exosome release of beta-catenin: a novel mechanism that antagonizes Wnt signaling J Cell Biol 2010 190 6 1079 1091 10.1083/jcb.201002049 20837771 PMC3101591 · DOI
  38. [41]Nazarenko I Rana S Baumann A McAlear J Hellwig A Trendelenburg M Lochnit G Preissner KT Zoller M Cell surface tetraspanin Tspan8 contributes to molecular pathways of exosome-induced endothelial cell activation Cancer Res 2010 70 4 1668 1678 10.1158/0008-5472.CAN-09-2470 20124479 · DOI
  39. [42]Hurwitz SN Conlon MM Rider MA Brownstein NC Meckes DG Jr Nanoparticle analysis sheds budding insights into genetic drivers of extracellular vesicle biogenesis J Extracell Vesicles 2016 5 31295 10.3402/jev.v5.31295 27421995 PMC4947197 · DOI
  40. [43]Hurwitz SN Nkosi D Conlon MM York SB Liu X Tremblay DC Meckes DG Jr CD63 regulates Epstein–Barr virus LMP1 exosomal packaging, enhancement of vesicle production, and noncanonical NF-kappaB signaling J Virol 2017 91 5 e01138–16 10.1128/JVI.02251-16 27974566 PMC5309960 · DOI
  41. [44]Zhu H, Guariglia S, Yu RY, Li W, Brancho D, Peinado H, Lyden D, Salzer J, Bennett C, Chow CW (2013) Mutation of SIMPLE in Charcot–Marie–Tooth 1C alters production of exosomes. Mol Biol Cell 24 (11):1619–1637, S1611–S1613. doi:10.1091/mbc.E12-07-0544 PMC3667717 23576546 · DOI
  42. [45]Brugger B Bankaitis VA Lipids and vesicular transport Biochim Biophys Acta 2012 1821 8 1039 10.1016/j.bbalip.2012.05.005 22659299 · DOI
  43. [46]McMahon HT Boucrot E Membrane curvature at a glance J Cell Sci 2015 128 6 1065 1070 10.1242/jcs.114454 25774051 PMC4359918 · DOI
  44. [47]Trajkovic K Hsu C Chiantia S Rajendran L Wenzel D Wieland F Schwille P Brugger B Simons M Ceramide triggers budding of exosome vesicles into multivesicular endosomes Science 2008 319 5867 1244 1247 10.1126/science.1153124 18309083 · DOI
  45. [49]Mittelbrunn M Gutierrez-Vazquez C Villarroya-Beltri C Gonzalez S Sanchez-Cabo F Gonzalez MA Bernad A Sanchez-Madrid F Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells Nat Commun 2011 2 282 10.1038/ncomms1285 21505438 PMC3104548 · DOI
  46. [50]Phuyal S Hessvik NP Skotland T Sandvig K Llorente A Regulation of exosome release by glycosphingolipids and flotillins FEBS J 2014 281 9 2214 2227 10.1111/febs.12775 24605801 · DOI
  47. [51]van Niel G Charrin S Simoes S Romao M Rochin L Saftig P Marks MS Rubinstein E Raposo G The tetraspanin CD63 regulates ESCRT-independent and -dependent endosomal sorting during melanogenesis Dev Cell 2011 21 4 708 721 10.1016/j.devcel.2011.08.019 21962903 PMC3199340 · DOI
  48. [52]Laulagnier K Grand D Dujardin A Hamdi S Vincent-Schneider H Lankar D Salles JP Bonnerot C Perret B Record M PLD2 is enriched on exosomes and its activity is correlated to the release of exosomes FEBS Lett 2004 572 1–3 11 14 10.1016/j.febslet.2004.06.082 15304316 · DOI
  49. [53]Ghossoub R Lembo F Rubio A Gaillard CB Bouchet J Vitale N Slavik J Machala M Zimmermann P Syntenin-ALIX exosome biogenesis and budding into multivesicular bodies are controlled by ARF6 and PLD2 Nat Commun 2014 5 3477 10.1038/ncomms4477 24637612 · DOI
  50. [54]Kooijman EE Chupin V de Kruijff B Burger KN Modulation of membrane curvature by phosphatidic acid and lysophosphatidic acid Traffic 2003 4 3 162 174 10.1034/j.1600-0854.2003.00086.x 12656989 · DOI
  51. [55]Alonso R Rodriguez MC Pindado J Merino E Merida I Izquierdo M Diacylglycerol kinase alpha regulates the secretion of lethal exosomes bearing Fas ligand during activation-induced cell death of T lymphocytes J Biol Chem 2005 280 31 28439 28450 10.1074/jbc.M501112200 15870081 · DOI
  52. [56]Alonso R Mazzeo C Rodriguez MC Marsh M Fraile-Ramos A Calvo V Avila-Flores A Merida I Izquierdo M Diacylglycerol kinase alpha regulates the formation and polarisation of mature multivesicular bodies involved in the secretion of Fas ligand-containing exosomes in T lymphocytes Cell Death Differ 2011 18 7 1161 1173 10.1038/cdd.2010.184 21252909 PMC3131963 · DOI
  53. [57]Mazzeo C Calvo V Alonso R Merida I Izquierdo M Protein kinase D1/2 is involved in the maturation of multivesicular bodies and secretion of exosomes in T and B lymphocytes Cell Death Differ 2016 23 1 99 109 10.1038/cdd.2015.72 26045048 PMC4815981 · DOI
  54. [58]Maas SL Breakefield XO Weaver AM Extracellular vesicles: unique intercellular delivery vehicles Trends Cell Biol 2017 27 3 172 188 10.1016/j.tcb.2016.11.003 27979573 PMC5318253 · DOI
  55. [59]Nolte-’t Hoen EN Buermans HP Waasdorp M Stoorvogel W Wauben MH t Hoen PA 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 2012 40 18 9272 9285 10.1093/nar/gks658 22821563 PMC3467056 · DOI
  56. [60]Pigati L Yaddanapudi SCS Iyengar R Kim D-J Hearn S Danforth D Hastings M Duelli D Selective release of microRNA species from normal and malignant mammary epithelial cells PLoS One 2010 5 10 e13515 e13515 10.1371/journal.pone.0013515 20976003 PMC2958125 · DOI
  57. [61]Hessvik NP Phuyal S Brech A Sandvig K Llorente A Profiling of microRNAs in exosomes released from PC-3 prostate cancer cells Biochim Biophys Acta 2012 1819 11–12 1154 1163 10.1016/j.bbagrm.2012.08.016 22982408 · DOI
  58. [62]Villarroya-Beltri C Gutierrez-Vazquez C Sanchez-Cabo F Perez-Hernandez D Vazquez J Martin-Cofreces N Martinez-Herrera DJ Pascual-Montano A Mittelbrunn M Sanchez-Madrid F Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs Nat Commun 2013 4 2980 10.1038/ncomms3980 24356509 PMC3905700 · DOI
  59. [63]Cha DJ Franklin JL Dou Y Liu Q Higginbotham JN Demory Beckler M Weaver AM Vickers K Prasad N Levy S Zhang B Coffey RJ Patton JG KRAS-dependent sorting of miRNA to exosomes eLife 2015 4 e07197 10.7554/eLife.07197 26132860 PMC4510696 · DOI
  60. [64]McKenzie AJ Hoshino D Hong NH Cha DJ Franklin JL Coffey RJ Patton JG Weaver AM KRAS-MEK signaling controls Ago2 sorting into exosomes Cell Rep 2016 15 5 978 987 10.1016/j.celrep.2016.03.085 27117408 PMC4857875 · DOI
  61. [65]Skog J Wurdinger T van Rijn S Meijer DH Gainche L Curry WT Carter BS Krichevsky AM Breakefield XO Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers Nat Cell Biol 2008 10 12 1470 1476 10.1038/ncb1800 19011622 PMC3423894 · DOI · Paper page
  62. [66]Batagov AO Kurochkin IV Exosomes secreted by human cells transport largely mRNA fragments that are enriched in the 3′-untranslated regions Biol Direct 2013 8 12 10.1186/1745-6150-8-12 23758897 PMC3732077 · DOI
  63. [67]Bolukbasi MF Mizrak A Ozdener GB Madlener S Strobel T Erkan EP Fan JB Breakefield XO Saydam O miR-1289 and “Zipcode”-like sequence enrich mRNAs in microvesicles Mol Ther Nucleic Acids 2012 1 e10 10.1038/mtna.2011.2 23344721 PMC3381601 · DOI
  64. [68]Buschow SI Liefhebber JM Wubbolts R Stoorvogel W Exosomes contain ubiquitinated proteins Blood Cells Mol Dis 2005 35 3 398 403 10.1016/j.bcmd.2005.08.005 16203162 · DOI
  65. [69]Smith VL Jackson L Schorey JS Ubiquitination as a mechanism to transport soluble mycobacterial and eukaryotic proteins to exosomes J Immunol 2015 195 6 2722 2730 10.4049/jimmunol.1403186 26246139 PMC5706551 · DOI
  66. [70]Cheng Y Schorey JS Targeting soluble proteins to exosomes using a ubiquitin tag Biotechnol Bioeng 2016 113 6 1315 1324 10.1002/bit.25884 26574179 · DOI
  67. [71]Skotland T Sandvig K Llorente A Lipids in exosomes: current knowledge and the way forward Prog Lipid Res 2017 66 30 41 10.1016/j.plipres.2017.03.001 28342835 · DOI · Paper page
  68. [72]Record M Poirot M Silvente-Poirot S Emerging concepts on the role of exosomes in lipid metabolic diseases Biochimie 2014 96 67 74 10.1016/j.biochi.2013.06.016 23827857 · DOI
  69. [73]Pike LJ Lipid rafts: bringing order to chaos J Lipid Res 2003 44 4 655 667 10.1194/jlr.R200021-JLR200 12562849 · DOI
  70. [74]Lingwood D Simons K Lipid rafts as a membrane-organizing principle Science 2010 327 5961 46 50 10.1126/science.1174621 20044567 · DOI · Paper page
  71. [75]de Gassart A Geminard C Fevrier B Raposo G Vidal M Lipid raft-associated protein sorting in exosomes Blood 2003 102 13 4336 4344 10.1182/blood-2003-03-0871 12881314 · DOI
  72. [76]Kajimoto T Okada T Miya S Zhang L Nakamura S Ongoing activation of sphingosine 1-phosphate receptors mediates maturation of exosomal multivesicular endosomes Nat Commun 2013 4 2712 10.1038/ncomms3712 24231649 · DOI
  73. [77]Villarroya-Beltri C Baixauli F Mittelbrunn M Fernandez-Delgado I Torralba D Moreno-Gonzalo O Baldanta S Enrich C Guerra S Sanchez-Madrid F ISGylation controls exosome secretion by promoting lysosomal degradation of MVB proteins Nat Commun 2016 7 13588 10.1038/ncomms13588 27882925 PMC5123068 · DOI
  74. [78]Villarroya-Beltri C Baixauli F Gutierrez-Vazquez C Sanchez-Madrid F Mittelbrunn M Sorting it out: regulation of exosome loading Semin Cancer Biol 2014 28 3 13 10.1016/j.semcancer.2014.04.009 24769058 PMC4640178 · DOI
  75. [79]Sinha S Hoshino D Hong NH Kirkbride KC Grega-Larson NE Seiki M Tyska MJ Weaver AM Cortactin promotes exosome secretion by controlling branched actin dynamics J Cell Biol 2016 214 2 197 213 10.1083/jcb.201601025 27402952 PMC4949450 · DOI
  76. [80]Stenmark H Rab GTPases as coordinators of vesicle traffic Nat Rev Mol Cell Biol 2009 10 8 513 525 10.1038/nrm2728 19603039 · DOI · Paper page
  77. [81]Savina A Vidal M Colombo MI The exosome pathway in K562 cells is regulated by Rab11 J Cell Sci 2002 115 Pt 12 2505 2515 12045221
  78. [82]Koles K Nunnari J Korkut C Barria R Brewer C Li Y Leszyk J Zhang B Budnik V Mechanism of evenness interrupted (Evi)-exosome release at synaptic boutons J Biol Chem 2012 287 20 16820 16834 10.1074/jbc.M112.342667 22437826 PMC3351299 · DOI
  79. [83]Ostrowski M, Carmo NB, Krumeich S, Fanget I, Raposo G, Savina A, Moita CF, Schauer K, Hume AN, Freitas RP, Goud B, Benaroch P, Hacohen N, Fukuda M, Desnos C, Seabra MC, Darchen F, Amigorena S, Moita LF, Thery C (2010) Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat Cell Biol 12(1):19–30; sup pp 11–13. doi:10.1038/ncb2000 19966785 · DOI
  80. [84]Hsu C Morohashi Y Yoshimura S Manrique-Hoyos N Jung S Lauterbach MA Bakhti M Gronborg M Mobius W Rhee J Barr FA Simons M Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C J Cell Biol 2010 189 2 223 232 10.1083/jcb.200911018 20404108 PMC2856897 · DOI
  81. [85]Fruhbeis C Frohlich D Kuo WP Amphornrat J Thilemann S Saab AS Kirchhoff F Mobius W Goebbels S Nave KA Schneider A Simons M Klugmann M Trotter J Kramer-Albers EM Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication PLoS Biol 2013 11 7 e1001604 10.1371/journal.pbio.1001604 23874151 PMC3706306 · DOI · Paper page
  82. [86]Bobrie A Krumeich S Reyal F Recchi C Moita LF Seabra MC Ostrowski M Thery C Rab27a supports exosome-dependent and -independent mechanisms that modify the tumor microenvironment and can promote tumor progression Cancer Res 2012 72 19 4920 4930 10.1158/0008-5472.CAN-12-0925 22865453 · DOI
  83. [87]Webber JP Spary LK Sanders AJ Chowdhury R Jiang WG Steadman R Wymant J Jones AT Kynaston H Mason MD Tabi Z Clayton A Differentiation of tumour-promoting stromal myofibroblasts by cancer exosomes Oncogene 2015 34 3 290 302 10.1038/onc.2013.560 24441045 · DOI
  84. [88]Abrami L Brandi L Moayeri M Brown MJ Krantz BA Leppla SH van der Goot FG Hijacking multivesicular bodies enables long-term and exosome-mediated long-distance action of anthrax toxin Cell Rep 2013 5 4 986 996 10.1016/j.celrep.2013.10.019 24239351 PMC3866279 · DOI
  85. [89]Jae N McEwan DG Manavski Y Boon RA Dimmeler S Rab7a and Rab27b control secretion of endothelial microRNA through extracellular vesicles FEBS Lett 2015 589 20 Pt B 3182 3188 10.1016/j.febslet.2015.08.040 26348397 · DOI
  86. [90]Worst TS Meyer Y Gottschalt M Weis CA von Hardenberg J Frank C Steidler A Michel MS Erben P RAB27A, RAB27B and VPS36 are downregulated in advanced prostate cancer and show functional relevance in prostate cancer cells Int J Oncol 2017 28197629
  87. [91]Loomis RJ Holmes DA Elms A Solski PA Der CJ Su L Citron kinase, a RhoA effector, enhances HIV-1 virion production by modulating exocytosis Traffic 2006 7 12 1643 1653 10.1111/j.1600-0854.2006.00503.x 17118119 PMC4420201 · DOI
  88. [92]Pfeffer SR Unsolved mysteries in membrane traffic Annu Rev Biochem 2007 76 629 645 10.1146/annurev.biochem.76.061705.130002 17263661 · DOI
  89. [93]Bonifacino JS Glick BS The mechanisms of vesicle budding and fusion Cell 2004 116 2 153 166 10.1016/S0092-8674(03)01079-1 14744428 · DOI
  90. [94]Fader CM Sanchez DG Mestre MB Colombo MI TI-VAMP/VAMP7 and VAMP3/cellubrevin: two v-SNARE proteins involved in specific steps of the autophagy/multivesicular body pathways Biochim Biophys Acta 2009 1793 12 1901 1916 10.1016/j.bbamcr.2009.09.011 19781582 · DOI
  91. [95]Ruiz-Martinez M Navarro A Marrades RM Vinolas N Santasusagna S Munoz C Ramirez J Molins L Monzo M YKT6 expression, exosome release, and survival in non-small cell lung cancer Oncotarget 2016 27285987 PMC5239493
  92. [96]Wei Y Wang D Jin F Bian Z Li L Liang H Li M Shi L Pan C Zhu D Chen X Hu G Liu Y Zhang CY Zen K Pyruvate kinase type M2 promotes tumour cell exosome release via phosphorylating synaptosome-associated protein 23 Nat Commun 2017 8 14041 10.1038/ncomms14041 28067230 PMC5228053 · DOI
  93. [97]Hyenne V Apaydin A Rodriguez D Spiegelhalter C Hoff-Yoessle S Diem M Tak S Lefebvre O Schwab Y Goetz JG Labouesse M RAL-1 controls multivesicular body biogenesis and exosome secretion J Cell Biol 2015 211 1 27 37 10.1083/jcb.201504136 26459596 PMC4602040 · DOI
  94. [98]Phuyal S Skotland T Hessvik NP Simolin H Overbye A Brech A Parton RG Ekroos K Sandvig K Llorente A The ether lipid precursor hexadecylglycerol stimulates the release and changes the composition of exosomes derived from PC-3 cells J Biol Chem 2015 13 290 4225 4237 10.1074/jbc.M114.593962 PMC4326831 25519911 · DOI
  95. [99]Glaser PE Gross RW Plasmenylethanolamine facilitates rapid membrane fusion: a stopped-flow kinetic investigation correlating the propensity of a major plasma membrane constituent to adopt an HII phase with its ability to promote membrane fusion Biochemistry 1994 33 19 5805 5812 10.1021/bi00185a019 8180209 · DOI
  96. [100]Strauss K Goebel C Runz H Mobius W Weiss S Feussner I Simons M Schneider A Exosome secretion ameliorates lysosomal storage of cholesterol in Niemann–Pick type C disease J Biol Chem 2010 285 34 26279 26288 10.1074/jbc.M110.134775 20554533 PMC2924046 · DOI
  97. [101]Llorente A van Deurs B Sandvig K Cholesterol regulates prostasome release from secretory lysosomes in PC-3 human prostate cancer cells Eur J Cell Biol 2007 86 7 405 415 10.1016/j.ejcb.2007.05.001 17601634 · DOI
  98. [102]Savina A Furlan M Vidal M Colombo MI Exosome release is regulated by a calcium-dependent mechanism in K562 cells J Biol Chem 2003 278 22 20083 20090 10.1074/jbc.M301642200 12639953 · DOI
  99. [103]Kramer-Albers EM Bretz N Tenzer S Winterstein C Mobius W Berger H Nave KA Schild H Trotter J Oligodendrocytes secrete exosomes containing major myelin and stress-protective proteins: trophic support for axons? Proteom Clin Appl 2007 1 11 1446 1461 10.1002/prca.200700522 21136642 · DOI
  100. [104]Tucker WC Chapman ER Role of synaptotagmin in Ca2+-triggered exocytosis Biochem J 2002 366 Pt 1 1 13 10.1042/bj20020776 12047220 PMC1222778 · DOI
  101. [106]Desdin-Mico G Mittelbrunn M Role of exosomes in the protection of cellular homeostasis Cell Adhes Migr 2016 PMC5351736 27875097
  102. [107]Lehmann BD Paine MS Brooks AM McCubrey JA Renegar RH Wang R Terrian DM Senescence-associated exosome release from human prostate cancer cells Cancer Res 2008 68 19 7864 7871 10.1158/0008-5472.CAN-07-6538 18829542 PMC3845029 · DOI · Paper page
  103. [108]Beer L Zimmermann M Mitterbauer A Ellinger A Gruber F Narzt MS Zellner M Gyongyosi M Madlener S Simader E Gabriel C Mildner M Ankersmit HJ Analysis of the secretome of apoptotic peripheral blood mononuclear cells: impact of released proteins and exosomes for tissue regeneration Sci Rep 2015 5 16662 10.1038/srep16662 26567861 PMC4645175 · DOI
  104. [109]Xiao X Yu S Li S Wu J Ma R Cao H Zhu Y Feng J Exosomes: decreased sensitivity of lung cancer A549 cells to cisplatin PLoS One 2014 9 2 e89534 10.1371/journal.pone.0089534 24586853 PMC3931805 · DOI
  105. [110]King HW Michael MZ Gleadle JM Hypoxic enhancement of exosome release by breast cancer cells BMC Cancer 2012 12 421 10.1186/1471-2407-12-421 22998595 PMC3488584 · DOI · Paper page
  106. [111]Kanemoto S Nitani R Murakami T Kaneko M Asada R Matsuhisa K Saito A Imaizumi K Multivesicular body formation enhancement and exosome release during endoplasmic reticulum stress Biochem Biophys Res Commun 2016 480 2 166 172 10.1016/j.bbrc.2016.10.019 27725157 · DOI
  107. [113]Fader CM Sanchez D Furlan M Colombo MI Induction of autophagy promotes fusion of multivesicular bodies with autophagic vacuoles in k562 cells Traffic 2008 9 2 230 250 10.1111/j.1600-0854.2007.00677.x 17999726 · DOI
  108. [114]Sahu R Kaushik S Clement CC Cannizzo ES Scharf B Follenzi A Potolicchio I Nieves E Cuervo AM Santambrogio L Microautophagy of cytosolic proteins by late endosomes Dev Cell 2011 20 1 131 139 10.1016/j.devcel.2010.12.003 21238931 PMC3025279 · DOI · Paper page
  109. [115]Alvarez-Erviti L Seow Y Schapira AH Gardiner C Sargent IL Wood MJ Cooper JM Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission Neurobiol Dis 2011 42 3 360 367 10.1016/j.nbd.2011.01.029 21303699 PMC3107939 · DOI
  110. [116]Murrow L Malhotra R Debnath J ATG12-ATG3 interacts with Alix to promote basal autophagic flux and late endosome function Nat Cell Biol 2015 17 3 300 310 10.1038/ncb3112 25686249 PMC4344874 · DOI
  111. [117]Ponpuak M Mandell MA Kimura T Chauhan S Cleyrat C Deretic V Secretory autophagy Curr Opin Cell Biol 2015 35 106 116 10.1016/j.ceb.2015.04.016 25988755 PMC4529791 · DOI
  112. [118]Ejlerskov P Rasmussen I Nielsen TT Bergstrom AL Tohyama Y Jensen PH Vilhardt F Tubulin polymerization-promoting protein (TPPP/p25alpha) promotes unconventional secretion of alpha-synuclein through exophagy by impairing autophagosome-lysosome fusion J Biol Chem 2013 288 24 17313 17335 10.1074/jbc.M112.401174 23629650 PMC3682534 · DOI
  113. [120]Settembre C Fraldi A Medina DL Ballabio A Signals from the lysosome: a control centre for cellular clearance and energy metabolism Nat Rev Mol Cell Biol 2013 14 5 283 296 10.1038/nrm3565 23609508 PMC4387238 · DOI
  114. [121]Van Deun J Mestdagh P Sormunen R Cocquyt V Vermaelen K Vandesompele J Bracke M De Wever O Hendrix A The impact of disparate isolation methods for extracellular vesicles on downstream RNA profiling J Extracell Vesicles 2014 25317274 PMC4169610
  115. [123]Coumans FAW Brisson AR Buzas EI Dignat-George F Drees EEE El-Andaloussi S Emanueli C Gasecka A Hendrix A Hill AF Lacroix R Lee Y van Leeuwen TG Mackman N Mager I Nolan JP van der Pol E Pegtel DM Sahoo S Siljander PRM Sturk G de Wever O Nieuwland R Methodological guidelines to study extracellular vesicles Circ Res 2017 120 10 1632 1648 10.1161/CIRCRESAHA.117.309417 28495994 · DOI
  116. [124]Szatanek R Baj-Krzyworzeka M Zimoch J Lekka M Siedlar M Baran J The methods of choice for extracellular vesicles (EVs) characterization Int J Mol Sci 2017 18 6 1153 10.3390/ijms18061153 28555055 PMC5485977 · DOI
  117. [125]Koritzinsky EH Street JM Star RA Yuen PS Quantification of exosomes J Cell Physiol 2017 232 7 1587 1590 10.1002/jcp.25387 27018079 PMC5039048 · DOI
  118. [126]Rupert DL Claudio V Lasser C Bally M Methods for the physical characterization and quantification of extracellular vesicles in biological samples Biochim Biophys Acta 2017 1861 1 Pt A 3164 3179 10.1016/j.bbagen.2016.07.028 27495390 · DOI
  119. [127]Hosseini-Beheshti E Pham S Adomat H Li N Tomlinson Guns ES Exosomes as biomarker enriched microvesicles: characterization of exosomal proteins derived from a panel of prostate cell lines with distinct AR phenotypes Mol Cell Proteom 2012 11 10 863 885 10.1074/mcp.M111.014845 PMC3494141 22723089 · DOI
  120. [128]Mathivanan S Lim JW Tauro BJ Ji H Moritz RL Simpson RJ Proteomics analysis of A33 immunoaffinity-purified exosomes released from the human colon tumor cell line LIM1215 reveals a tissue-specific protein signature Mol Cell Proteom 2010 9 2 197 208 10.1074/mcp.M900152-MCP200 PMC2830834 19837982 · DOI
  121. [129]Tauro BJ Greening DW Mathias RA Ji H Mathivanan S Scott AM Simpson RJ Comparison of ultracentrifugation, density gradient separation, and immunoaffinity capture methods for isolating human colon cancer cell line LIM1863-derived exosomes Methods 2012 56 2 293 304 10.1016/j.ymeth.2012.01.002 22285593 · DOI
  122. [130]Rupert DL Shelke GV Emilsson G Claudio V Block S Lasser C Dahlin A Lotvall JO Bally M Zhdanov VP Hook F Dual-wavelength surface plasmon resonance for determining the size and concentration of sub-populations of extracellular vesicles Anal Chem 2016 27644331
  123. [131]Grasso L Wyss R Weidenauer L Thampi A Demurtas D Prudent M Lion N Vogel H Molecular screening of cancer-derived exosomes by surface plasmon resonance spectroscopy Anal Bioanal Chem 2015 407 18 5425 5432 10.1007/s00216-015-8711-5 25925862 PMC4477949 · DOI
  124. [132]Sina AA Vaidyanathan R Dey S Carrascosa LG Shiddiky MJ Trau M Real time and label free profiling of clinically relevant exosomes Sci Rep 2016 6 30460 10.1038/srep30460 27464736 PMC4964344 · DOI
  125. [133]Osteikoetxea X Balogh A Szabo-Taylor K Nemeth A Szabo TG Paloczi K Sodar B Kittel A Gyorgy B Pallinger E Matko J Buzas EI Improved characterization of EV preparations based on protein to lipid ratio and lipid properties PLoS One 2015 10 3 e0121184 10.1371/journal.pone.0121184 25798862 PMC4370721 · DOI
  126. [135]Nolte-’t Hoen EN van der Vlist EJ Aalberts M Mertens HC Bosch BJ Bartelink W Mastrobattista E van Gaal EV Stoorvogel W Arkesteijn GJ Wauben MH Quantitative and qualitative flow cytometric analysis of nanosized cell-derived membrane vesicles Nanomed Nanotechnol Biol Med 2012 8 5 712 720 10.1016/j.nano.2011.09.006 PMC7106164 22024193 · DOI
  127. [136]Sokolova V Ludwig AK Hornung S Rotan O Horn PA Epple M Giebel B Characterisation of exosomes derived from human cells by nanoparticle tracking analysis and scanning electron microscopy Colloids Surf B 2011 87 1 146 150 10.1016/j.colsurfb.2011.05.013 21640565 · DOI
  128. [137]Dragovic RA Gardiner C Brooks AS Tannetta DS Ferguson DJ Hole P Carr B Redman CW Harris AL Dobson PJ Harrison P Sargent IL Sizing and phenotyping of cellular vesicles using Nanoparticle Tracking Analysis Nanomed Nanotechnol Biol Med 2011 7 6 780 788 10.1016/j.nano.2011.04.003 PMC3280380 21601655 · DOI
  129. [138]Maas SL Broekman ML de Vrij J Tunable resistive pulse sensing for the characterization of extracellular vesicles Methods Mol Biol (Clifton, NJ) 2017 1545 21 33 10.1007/978-1-4939-6728-5_2 27943204 · DOI
  130. [139]Lerner N Avissar S Beit-Yannai E Extracellular vesicles mediate signaling between the aqueous humor producing and draining cells in the ocular system PLoS One 2017 12 2 e0171153 10.1371/journal.pone.0171153 28241021 PMC5328276 · DOI

Cited by

Sorted by citations

Authors
Hessvik, N. P., & Llorente, A.
Affiliations
Oslo University Hospital (NO)
Corresponding author
Llorente, Alicia
ORCID
Llorente, Alicia
Venue
Cellular and Molecular Life Sciences
Publisher
Springer Science and Business Media LLC
Published
2017-07-21
Volume
75
Issue
2
Pages
193-208
ISSN
  • 1420-682X (ISSN-L)
  • 1420-9071
DOI
10.1007/s00018-017-2595-9
PMC
PMC5756260
OpenAlex
W2738491178
Cited by
2,362
References
9
Citations by year
2026: 150 · 2025: 207 · 2024: 318 · 2023: 313 · 2022: 372 · 2021: 347 · 2020: 361 · 2019: 210 · 2018: 76 · 2017: 8
FWCI
16.77
Type
journal article
Language
en
Open access
Licence
Locations
  • Cellular and Molecular Life Sciences (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Kreftforeningen
  • The Research Council of Norway (179571)
  • The Norwegian Financial Mechanism (NFI/R/2014/045)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
Keywords
exosomes, exosome biogenesis, exosome secretion, multivesicular bodies, endocytic pathway, cell-to-cell communication, autophagy, lysosomal exocytosis, exosome isolation methods, exosome therapy, exosome-based diagnosis
MeSH terms
Animals, Autophagy, Biological Transport, Cell Membrane, Exocytosis, Humans, Lysosomes, Membrane Fusion, Exosomes, Multivesicular Bodies

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