Extracellular Vesicles as Delivery Vehicles of Specific Cellular Cargo
Abstract
:1. Introduction
2. Heterogeneity of Extracellular Vesicles (EVs)
3. Mechanism of Cargo Sorting into EVs
3.1. Pathways of Protein Sorting
3.2. The Role of Lipids in EV Formation
3.3. Transfer of RNA between Cells
3.4. Transfer of Mitochondrial DNA
3.5. Foreign Molecules
3.6. Mineral Crystals as Cargo of Calcifying EVs
4. Phosphoinositides Determine the Fate of Intraluminal Vesicles
5. Inhibition and Promotion of EV Release for Therapeutic Approaches
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- McGough, I.J.; Vincent, J.P. Exosomes in developmental signalling. Development 2016, 143, 2482–2493. [Google Scholar] [CrossRef] [Green Version]
- Buschow, S.I.; Nolte-’t Hoen, E.N.; van Niel, G.; Pols, M.S.; ten Broeke, T.; Lauwen, M.; Ossendorp, F.; Melief, C.J.; Raposo, G.; Wubbolts, R.; et al. MHC II in dendritic cells is targeted to lysosomes or T cell-induced exosomes via distinct multivesicular body pathways. Traffic 2009, 10, 1528–1542. [Google Scholar] [CrossRef] [PubMed]
- Thery, C.; Regnault, A.; Garin, J.; Wolfers, J.; Zitvogel, L.; Ricciardi-Castagnoli, P.; Raposo, G.; Amigorena, S. Molecular characterization of dendritic cell-derived exosomes. Selective accumulation of the heat shock protein hsc73. J. Cell. Biol. 1999, 147, 599–610. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Anderson, M.R.; Kashanchi, F.; Jacobson, S. Exosomes in Viral Disease. Neurotherapeutics 2016, 13, 535–546. [Google Scholar] [CrossRef]
- Zhou, X.; Zhang, W.; Yao, Q.; Zhang, H.; Dong, G.; Zhang, M.; Liu, Y.; Chen, J.K.; Dong, Z. Exosome production and its regulation of EGFR during wound healing in renal tubular cells. Am. J. Physiol. Renal Physiol. 2017, 312, F963–F970. [Google Scholar] [CrossRef]
- Zhang, H.; Deng, T.; Liu, R.; Bai, M.; Zhou, L.; Wang, X.; Li, S.; Wang, X.; Yang, H.; Li, J.; et al. Exosome-delivered EGFR regulates liver microenvironment to promote gastric cancer liver metastasis. Nat. Commun. 2017, 8, 15016. [Google Scholar] [CrossRef] [Green Version]
- Abd Elmageed, Z.Y.; Yang, Y.; Thomas, R.; Ranjan, M.; Mondal, D.; Moroz, K.; Fang, Z.; Rezk, B.M.; Moparty, K.; Sikka, S.C.; et al. Neoplastic reprogramming of patient-derived adipose stem cells by prostate cancer cell-associated exosomes. Stem Cells 2014, 32, 983–997. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Coleman, B.M.; Hill, A.F. Extracellular vesicles--Their role in the packaging and spread of misfolded proteins associated with neurodegenerative diseases. Semin. Cell. Dev. Biol. 2015, 40, 89–96. [Google Scholar] [CrossRef] [PubMed]
- Fruhbeis, C.; Frohlich, D.; Kuo, W.P.; Kramer-Albers, E.M. Extracellular vesicles as mediators of neuron-glia communication. Front. Cell. Neurosci. 2013, 7, 182. [Google Scholar] [CrossRef] [Green Version]
- Cappariello, A.; Loftus, A.; Muraca, M.; Maurizi, A.; Rucci, N.; Teti, A. Osteoblast-Derived Extracellular Vesicles Are Biological Tools for the Delivery of Active Molecules to Bone. J. Bone Miner. Res. 2018, 33, 517–533. [Google Scholar] [CrossRef] [Green Version]
- Hutcheson, J.D.; Goettsch, C.; Bertazzo, S.; Maldonado, N.; Ruiz, J.L.; Goh, W.; Yabusaki, K.; Faits, T.; Bouten, C.; Franck, G.; et al. Genesis and growth of extracellular-vesicle-derived microcalcification in atherosclerotic plaques. Nat. Mater. 2016, 15, 335–343. [Google Scholar] [CrossRef] [Green Version]
- van der Pol, E.; Boing, A.N.; Gool, E.L.; Nieuwland, R. Recent developments in the nomenclature, presence, isolation, detection and clinical impact of extracellular vesicles. J. Thromb. Haemost. 2016, 14, 48–56. [Google Scholar] [CrossRef] [Green Version]
- Araldi, E.; Kramer-Albers, E.M.; Hoen, E.N.; Peinado, H.; Psonka-Antonczyk, K.M.; Rao, P.; van Niel, G.; Yanez-Mo, M.; Nazarenko, I. International Society for Extracellular Vesicles: First annual meeting, April 17–21, 2012: ISEV-2012. J. Extracell. Vesicles 2012, 1, 19995. [Google Scholar] [CrossRef]
- Thery, C.; Witwer, K.W.; Aikawa, E.; Alcaraz, M.J.; Anderson, J.D.; Andriantsitohaina, R.; Antoniou, A.; Arab, T.; Archer, F.; Atkin-Smith, G.K.; et al. Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines. J. Extracell. Vesicles 2018, 7, 1535750. [Google Scholar] [CrossRef] [Green Version]
- Athman, J.J.; Wang, Y.; McDonald, D.J.; Boom, W.H.; Harding, C.V.; Wearsch, P.A. Bacterial Membrane Vesicles Mediate the Release of Mycobacterium tuberculosis Lipoglycans and Lipoproteins from Infected Macrophages. J. Immunol. 2015, 195, 1044–1053. [Google Scholar] [CrossRef] [Green Version]
- Kowal, J.; Arras, G.; Colombo, M.; Jouve, M.; Morath, J.P.; Primdal-Bengtson, B.; Dingli, F.; Loew, D.; Tkach, M.; Thery, C. Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. Proc. Natl. Acad. Sci. USA 2016, 113, E968–E977. [Google Scholar] [CrossRef] [Green Version]
- Zhang, H.; Freitas, D.; Kim, H.S.; Fabijanic, K.; Li, Z.; Chen, H.; Mark, M.T.; Molina, H.; Martin, A.B.; Bojmar, L.; et al. Identification of distinct nanoparticles and subsets of extracellular vesicles by asymmetric flow field-flow fractionation. Nat. Cell. Biol. 2018, 20, 332–343. [Google Scholar] [CrossRef]
- Zhang, Q.; Higginbotham, J.N.; Jeppesen, D.K.; Yang, Y.P.; Li, W.; McKinley, E.T.; Graves-Deal, R.; Ping, J.; Britain, C.M.; Dorsett, K.A.; et al. Transfer of Functional Cargo in Exomeres. Cell Rep. 2019, 27, 940–954.e946. [Google Scholar] [CrossRef] [Green Version]
- Larson, M.C.; Woodliff, J.E.; Hillery, C.A.; Kearl, T.J.; Zhao, M. Phosphatidylethanolamine is externalized at the surface of microparticles. Biochim. Biophys. Acta 2012, 1821, 1501–1507. [Google Scholar] [CrossRef] [Green Version]
- Cosenza, S.; Toupet, K.; Maumus, M.; Luz-Crawford, P.; Blanc-Brude, O.; Jorgensen, C.; Noel, D. Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis. Theranostics 2018, 8, 1399–1410. [Google Scholar] [CrossRef] [PubMed]
- Brites, D.; Fernandes, A. Neuroinflammation and Depression: Microglia Activation, Extracellular Microvesicles and microRNA Dysregulation. Front. Cell. Neurosci. 2015, 9, 476. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jeppesen, D.K.; Fenix, A.M.; Franklin, J.L.; Higginbotham, J.N.; Zhang, Q.; Zimmerman, L.J.; Liebler, D.C.; Ping, J.; Liu, Q.; Evans, R.; et al. Reassessment of Exosome Composition. Cell 2019, 177, 428–445 e418. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Piccin, A.; Murphy, W.G.; Smith, O.P. Circulating microparticles: Pathophysiology and clinical implications. Blood Rev. 2007, 21, 157–171. [Google Scholar] [CrossRef]
- Atkin-Smith, G.K.; Tixeira, R.; Paone, S.; Mathivanan, S.; Collins, C.; Liem, M.; Goodall, K.J.; Ravichandran, K.S.; Hulett, M.D.; Poon, I.K. A novel mechanism of generating extracellular vesicles during apoptosis via a beads-on-a-string membrane structure. Nat. Commun. 2015, 6, 7439. [Google Scholar] [CrossRef]
- Atkin-Smith, G.K.; Paone, S.; Zanker, D.J.; Duan, M.; Phan, T.K.; Chen, W.; Hulett, M.D.; Poon, I.K. Isolation of cell type-specific apoptotic bodies by fluorescence-activated cell sorting. Sci. Rep. 2017, 7, 39846. [Google Scholar] [CrossRef]
- Huang, P.H.; Huang, S.S.; Chen, Y.H.; Lin, C.P.; Chiang, K.H.; Chen, J.S.; Tsai, H.Y.; Lin, F.Y.; Chen, J.W.; Lin, S.J. Increased circulating CD31+/annexin V+ apoptotic microparticles and decreased circulating endothelial progenitor cell levels in hypertensive patients with microalbuminuria. J. Hypertens. 2010, 28, 1655–1665. [Google Scholar] [CrossRef]
- Osteikoetxea, X.; Nemeth, A.; Sodar, B.W.; Vukman, K.V.; Buzas, E.I. Extracellular vesicles in cardiovascular disease: Are they Jedi or Sith? J. Physiol. 2016, 594, 2881–2894. [Google Scholar] [CrossRef] [Green Version]
- Boing, A.N.; van der Pol, E.; Grootemaat, A.E.; Coumans, F.A.; Sturk, A.; Nieuwland, R. Single-step isolation of extracellular vesicles by size-exclusion chromatography. J. Extracell. Vesicles 2014, 3. [Google Scholar] [CrossRef]
- Wang, W.; Luo, J.; Wang, S. Recent Progress in Isolation and Detection of Extracellular Vesicles for Cancer Diagnostics. Adv. Healthc. Mater 2018, 7, e1800484. [Google Scholar] [CrossRef]
- Wiklander, O.P.B.; Bostancioglu, R.B.; Welsh, J.A.; Zickler, A.M.; Murke, F.; Corso, G.; Felldin, U.; Hagey, D.W.; Evertsson, B.; Liang, X.M.; et al. Systematic Methodological Evaluation of a Multiplex Bead-Based Flow Cytometry Assay for Detection of Extracellular Vesicle Surface Signatures. Front. Immunol. 2018, 9, 1326. [Google Scholar] [CrossRef] [Green Version]
- Campos-Silva, C.; Suarez, H.; Jara-Acevedo, R.; Linares-Espinos, E.; Martinez-Pineiro, L.; Yanez-Mo, M.; Vales-Gomez, M. High sensitivity detection of extracellular vesicles immune-captured from urine by conventional flow cytometry. Sci. Rep. 2019, 9, 2042. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pospichalova, V.; Svoboda, J.; Dave, Z.; Kotrbova, A.; Kaiser, K.; Klemova, D.; Ilkovics, L.; Hampl, A.; Crha, I.; Jandakova, E.; et al. Simplified protocol for flow cytometry analysis of fluorescently labeled exosomes and microvesicles using dedicated flow cytometer. J. Extracell. Vesicles 2015, 4, 25530. [Google Scholar] [CrossRef] [PubMed]
- Gidlof, O.; Evander, M.; Rezeli, M.; Marko-Varga, G.; Laurell, T.; Erlinge, D. Proteomic profiling of extracellular vesicles reveals additional diagnostic biomarkers for myocardial infarction compared to plasma alone. Sci. Rep. 2019, 9, 8991. [Google Scholar] [CrossRef] [Green Version]
- Katzmann, D.J.; Babst, M.; Emr, S.D. Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell 2001, 106, 145–155. [Google Scholar] [CrossRef] [Green Version]
- 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. [Google Scholar] [CrossRef] [Green Version]
- Ageta, H.; Ageta-Ishihara, N.; Hitachi, K.; Karayel, O.; Onouchi, T.; Yamaguchi, H.; Kahyo, T.; Hatanaka, K.; Ikegami, K.; Yoshioka, Y.; et al. UBL3 modification influences protein sorting to small extracellular vesicles. Nat. Commun. 2018, 9, 3936. [Google Scholar] [CrossRef]
- Dores, M.R.; Chen, B.; Lin, H.; Soh, U.J.; Paing, M.M.; Montagne, W.A.; Meerloo, T.; Trejo, J. ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting. J. Cell. Biol. 2012, 197, 407–419. [Google Scholar] [CrossRef]
- Roucourt, B.; Meeussen, S.; Bao, J.; Zimmermann, P.; David, G. Heparanase activates the syndecan-syntenin-ALIX exosome pathway. Cell. Res. 2015, 25, 412–428. [Google Scholar] [CrossRef] [Green Version]
- Putz, U.; Howitt, J.; Lackovic, J.; Foot, N.; Kumar, S.; Silke, J.; Tan, S.S. Nedd4 family-interacting protein 1 (Ndfip1) is required for the exosomal secretion of Nedd4 family proteins. J. Biol. Chem. 2008, 283, 32621–32627. [Google Scholar] [CrossRef] [Green Version]
- Sterzenbach, U.; Putz, U.; Low, L.H.; Silke, J.; Tan, S.S.; Howitt, J. Engineered Exosomes as Vehicles for Biologically Active Proteins. Mol. Ther. 2017, 25, 1269–1278. [Google Scholar] [CrossRef] [Green Version]
- 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. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mazurov, D.; Barbashova, L.; Filatov, A. Tetraspanin protein CD9 interacts with metalloprotease CD10 and enhances its release via exosomes. FEBS J. 2013, 280, 1200–1213. [Google Scholar] [CrossRef]
- van Niel, G.; Charrin, S.; Simoes, S.; Romao, M.; Rochin, L.; Saftig, P.; Marks, M.S.; Rubinstein, E.; Raposo, G. The tetraspanin CD63 regulates ESCRT-independent and -dependent endosomal sorting during melanogenesis. Dev. Cell. 2011, 21, 708–721. [Google Scholar] [CrossRef] [Green Version]
- Nabhan, J.F.; Hu, R.; Oh, R.S.; Cohen, S.N.; Lu, Q. 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 2012, 109, 4146–4151. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gangalum, R.K.; Atanasov, I.C.; Zhou, Z.H.; Bhat, S.P. AlphaB-crystallin is found in detergent-resistant membrane microdomains and is secreted via exosomes from human retinal pigment epithelial cells. J Biol. Chem. 2011, 286, 3261–3269. [Google Scholar] [CrossRef] [Green Version]
- Li, S.P.; Lin, Z.X.; Jiang, X.Y.; Yu, X.Y. Exosomal cargo-loading and synthetic exosome-mimics as potential therapeutic tools. Acta Pharmacol. Sin. 2018, 39, 542–551. [Google Scholar] [CrossRef] [Green Version]
- Villarroya-Beltri, C.; Gutierrez-Vazquez, C.; Sanchez-Cabo, F.; Perez-Hernandez, D.; Vazquez, J.; Martin-Cofreces, N.; Martinez-Herrera, D.J.; 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. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Santangelo, L.; Giurato, G.; Cicchini, C.; Montaldo, C.; Mancone, C.; Tarallo, R.; Battistelli, C.; Alonzi, T.; Weisz, A.; Tripodi, M. The RNA-Binding Protein SYNCRIP Is a Component of the Hepatocyte Exosomal Machinery Controlling MicroRNA Sorting. Cell Rep. 2016, 17, 799–808. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Iavello, A.; Frech, V.S.; Gai, C.; Deregibus, M.C.; Quesenberry, P.J.; Camussi, G. Role of Alix in miRNA packaging during extracellular vesicle biogenesis. Int. J. Mol. Med. 2016, 37, 958–966. [Google Scholar] [CrossRef] [Green Version]
- Cha, D.J.; Franklin, J.L.; Dou, Y.; Liu, Q.; Higginbotham, J.N.; Demory Beckler, M.; Weaver, A.M.; Vickers, K.; Prasad, N.; Levy, S.; et al. KRAS-dependent sorting of miRNA to exosomes. Elife 2015, 4, e07197. [Google Scholar] [CrossRef]
- Shurtleff, M.J.; Temoche-Diaz, M.M.; Karfilis, K.V.; Ri, S.; Schekman, R. Y-box protein 1 is required to sort microRNAs into exosomes in cells and in a cell-free reaction. Elife 2016, 5. [Google Scholar] [CrossRef] [PubMed]
- Mukherjee, K.; Ghoshal, B.; Ghosh, S.; Chakrabarty, Y.; Shwetha, S.; Das, S.; Bhattacharyya, S.N. Reversible HuR-microRNA binding controls extracellular export of miR-122 and augments stress response. EMBO Rep. 2016, 17, 1184–1203. [Google Scholar] [CrossRef] [PubMed]
- Leidal, A.M.; Huang, H.H.; Marsh, T.; Solvik, T.; Zhang, D.; Ye, J.; Kai, F.; Goldsmith, J.; Liu, J.Y.; Huang, Y.H.; et al. The LC3-conjugation machinery specifies the loading of RNA-binding proteins into extracellular vesicles. Nat. Cell. Biol. 2020, 22, 187–199. [Google Scholar] [CrossRef]
- Sansone, P.; Savini, C.; Kurelac, I.; Chang, Q.; Amato, L.B.; Strillacci, A.; Stepanova, A.; Iommarini, L.; Mastroleo, C.; Daly, L.; et al. Packaging and transfer of mitochondrial DNA via exosomes regulate escape from dormancy in hormonal therapy-resistant breast cancer. Proc. Natl. Acad. Sci. USA 2017, 114, E9066–E9075. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kapustin, A.N.; Chatrou, M.L.; Drozdov, I.; Zheng, Y.; Davidson, S.M.; Soong, D.; Furmanik, M.; Sanchis, P.; De Rosales, R.T.; Alvarez-Hernandez, D.; et al. Vascular smooth muscle cell calcification is mediated by regulated exosome secretion. Circ. Res. 2015, 116, 1312–1323. [Google Scholar] [CrossRef] [Green Version]
- Wuthier, R.E.; Wu, L.N.; Sauer, G.R.; Genge, B.R.; Yoshimori, T.; Ishikawa, Y. Mechanism of matrix vesicle calcification: Characterization of ion channels and the nucleational core of growth plate vesicles. Bone Miner. 1992, 17, 290–295. [Google Scholar] [CrossRef]
- Raposo, G.; Stoorvogel, W. Extracellular vesicles: Exosomes, microvesicles, and friends. J. Cell. Biol. 2013, 200, 373–383. [Google Scholar] [CrossRef] [Green Version]
- Frankel, E.B.; Audhya, A. ESCRT-dependent cargo sorting at multivesicular endosomes. Semin. Cell Dev. Biol. 2018, 74, 4–10. [Google Scholar] [CrossRef]
- Norris, A.; Tammineni, P.; Wang, S.; Gerdes, J.; Murr, A.; Kwan, K.Y.; Cai, Q.; Grant, B.D. SNX-1 and RME-8 oppose the assembly of HGRS-1/ESCRT-0 degradative microdomains on endosomes. Proc. Natl. Acad. Sci. USA 2017, 114, E307–E316. [Google Scholar] [CrossRef] [Green Version]
- Gillooly, D.J.; Raiborg, C.; Stenmark, H. Phosphatidylinositol 3-phosphate is found in microdomains of early endosomes. Histochem. Cell. Biol. 2003, 120, 445–453. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Boura, E.; Ivanov, V.; Carlson, L.A.; Mizuuchi, K.; Hurley, J.H. Endosomal sorting complex required for transport (ESCRT) complexes induce phase-separated microdomains in supported lipid bilayers. J. Biol. Chem. 2012, 287, 28144–28151. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Teo, H.; Perisic, O.; Gonzalez, B.; Williams, R.L. ESCRT-II, an endosome-associated complex required for protein sorting: Crystal structure and interactions with ESCRT-III and membranes. Dev. Cell. 2004, 7, 559–569. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hurley, J.H.; Boura, E.; Carlson, L.A.; Rozycki, B. Membrane budding. Cell 2010, 143, 875–887. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Agromayor, M.; Martin-Serrano, J. Interaction of AMSH with ESCRT-III and deubiquitination of endosomal cargo. J. Biol. Chem. 2006, 281, 23083–23091. [Google Scholar] [CrossRef] [Green Version]
- Sun, S.; Zhou, X.; Zhang, W.; Gallick, G.E.; Kuang, J. Unravelling the pivotal role of Alix in MVB sorting and silencing of the activated EGFR. Biochem. J. 2015, 466, 475–487. [Google Scholar] [CrossRef] [Green Version]
- Dores, M.R.; Grimsey, N.J.; Mendez, F.; Trejo, J. ALIX Regulates the Ubiquitin-Independent Lysosomal Sorting of the P2Y1 Purinergic Receptor via a YPX3L Motif. PLoS ONE 2016, 11, e0157587. [Google Scholar] [CrossRef]
- Geminard, C.; De Gassart, A.; Blanc, L.; Vidal, M. Degradation of AP2 during reticulocyte maturation enhances binding of hsc70 and Alix to a common site on TFR for sorting into exosomes. Traffic 2004, 5, 181–193. [Google Scholar] [CrossRef]
- Matsuo, H.; Chevallier, J.; Mayran, N.; Le Blanc, I.; Ferguson, C.; Faure, J.; Blanc, N.S.; Matile, S.; Dubochet, J.; Sadoul, R.; et al. Role of LBPA and Alix in multivesicular liposome formation and endosome organization. Science 2004, 303, 531–534. [Google Scholar] [CrossRef]
- Baietti, M.F.; Zhang, Z.; Mortier, E.; Melchior, A.; Degeest, G.; Geeraerts, A.; Ivarsson, Y.; Depoortere, F.; Coomans, C.; Vermeiren, E.; et al. Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat. Cell. Biol. 2012, 14, 677–685. [Google Scholar] [CrossRef]
- Friand, V.; David, G.; Zimmermann, P. Syntenin and syndecan in the biogenesis of exosomes. Biol. Cell 2015, 107, 331–341. [Google Scholar] [CrossRef]
- Stuffers, S.; Sem Wegner, C.; Stenmark, H.; Brech, A. Multivesicular endosome biogenesis in the absence of ESCRTs. Traffic 2009, 10, 925–937. [Google Scholar] [CrossRef]
- Edgar, J.R.; Eden, E.R.; Futter, C.E. Hrs- and CD63-dependent competing mechanisms make different sized endosomal intraluminal vesicles. Traffic 2014, 15, 197–211. [Google Scholar] [CrossRef]
- 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, 1244–1247. [Google Scholar] [CrossRef] [PubMed]
- Mobius, W.; Ohno-Iwashita, Y.; van Donselaar, E.G.; Oorschot, V.M.; Shimada, Y.; Fujimoto, T.; Heijnen, H.F.; Geuze, H.J.; Slot, J.W. Immunoelectron microscopic localization of cholesterol using biotinylated and non-cytolytic perfringolysin O. J. Histochem. Cytochem. 2002, 50, 43–55. [Google Scholar] [CrossRef]
- Harada, Y.; Suzuki, T.; Fukushige, T.; Kizuka, Y.; Yagi, H.; Yamamoto, M.; Kondo, K.; Inoue, H.; Kato, K.; Taniguchi, N.; et al. Generation of the heterogeneity of extracellular vesicles by membrane organization and sorting machineries. Biochim. Biophys. Acta 2019, 1863, 681–691. [Google Scholar] [CrossRef] [PubMed]
- Ghossoub, R.; Lembo, F.; Rubio, A.; Gaillard, C.B.; 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. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Juan, T.; Fürthauer, M. Biogenesis and function of ESCRT-dependent extracellular vesicles. Semin. Cell. Dev. Biol. 2017, 74, 66–77. [Google Scholar] [CrossRef] [PubMed]
- Koppers-Lalic, D.; Hackenberg, M.; Bijnsdorp, I.V.; van Eijndhoven, M.A.J.; Sadek, P.; Sie, D.; Zini, N.; Middeldorp, J.M.; Ylstra, B.; de Menezes, R.X.; et al. Nontemplated nucleotide additions distinguish the small RNA composition in cells from exosomes. Cell Rep. 2014, 8, 1649–1658. [Google Scholar] [CrossRef] [Green Version]
- Nolte-’t Hoen, E.N.; Buermans, H.P.; Waasdorp, M.; Stoorvogel, W.; Wauben, M.H.; t Hoen, P.A. 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, 9272–9285. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mittelbrunn, M.; Gutierrez-Vazquez, C.; Villarroya-Beltri, C.; Gonzalez, S.; Sanchez-Cabo, F.; Gonzalez, M.A.; Bernad, A.; Sanchez-Madrid, F. Unidirectional transfer of microRNA-loaded exosomes from T cells to antigen-presenting cells. Nat. Commun. 2011, 2, 282. [Google Scholar] [CrossRef] [Green Version]
- Tran, N. Cancer Exosomes as miRNA Factories. Trends Cancer 2016, 2, 329–331. [Google Scholar] [CrossRef] [PubMed]
- Gibbings, D.J.; Ciaudo, C.; Erhardt, M.; Voinnet, O. Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nat. Cell. Biol. 2009, 11, 1143–1149. [Google Scholar] [CrossRef] [PubMed]
- Kosaka, N.; Iguchi, H.; Yoshioka, Y.; Takeshita, F.; Matsuki, Y.; Ochiya, T. Secretory mechanisms and intercellular transfer of microRNAs in living cells. J. Biol. Chem. 2010, 285, 17442–17452. [Google Scholar] [CrossRef] [Green Version]
- Spees, J.L.; Olson, S.D.; Whitney, M.J.; Prockop, D.J. Mitochondrial transfer between cells can rescue aerobic respiration. Proc. Natl. Acad. Sci. USA 2006, 103, 1283–1288. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Phinney, D.G.; Di Giuseppe, M.; Njah, J.; Sala, E.; Shiva, S.; St Croix, C.M.; Stolz, D.B.; Watkins, S.C.; Di, Y.P.; Leikauf, G.D.; et al. Mesenchymal stem cells use extracellular vesicles to outsource mitophagy and shuttle microRNAs. Nat. Commun. 2015, 6, 8472. [Google Scholar] [CrossRef] [PubMed]
- Longatti, A.; Boyd, B.; Chisari, F.V. Virion-independent transfer of replication-competent hepatitis C virus RNA between permissive cells. J. Virol. 2015, 89, 2956–2961. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Longatti, A. The Dual Role of Exosomes in Hepatitis A and C Virus Transmission and Viral Immune Activation. Viruses 2015, 7, 6707–6715. [Google Scholar] [CrossRef] [Green Version]
- Hoshina, S.; Sekizuka, T.; Kataoka, M.; Hasegawa, H.; Hamada, H.; Kuroda, M.; Katano, H. Profile of Exosomal and Intracellular microRNA in Gamma-Herpesvirus-Infected Lymphoma Cell Lines. PLoS ONE 2016, 11, e0162574. [Google Scholar] [CrossRef] [Green Version]
- Gallo, A.; Vella, S.; Miele, M.; Timoneri, F.; Di Bella, M.; Bosi, S.; Sciveres, M.; Conaldi, P.G. Global profiling of viral and cellular non-coding RNAs in Epstein-Barr virus-induced lymphoblastoid cell lines and released exosome cargos. Cancer Lett. 2017, 388, 334–343. [Google Scholar] [CrossRef]
- Flanagan, J.; Middeldorp, J.; Sculley, T. Localization of the Epstein-Barr virus protein LMP 1 to exosomes. J. Gen. Virol. 2003, 84, 1871–1879. [Google Scholar] [CrossRef]
- Temme, S.; Eis-Hubinger, A.M.; McLellan, A.D.; Koch, N. The herpes simplex virus-1 encoded glycoprotein B diverts HLA-DR into the exosome pathway. J. Immunol. 2010, 184, 236–243. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Khan, G.; Ahmed, W.; Philip, P.S. Exosomes and Their Role in Viral Infections. In Novel Implications of Exosomes in Diagnosis and Treatment of Cancer and Infectious Diseases; InTech: London, UK, 2017. [Google Scholar] [CrossRef] [Green Version]
- Gould, S.J.; Booth, A.M.; Hildreth, J.E. The Trojan exosome hypothesis. Proc. Natl. Acad. Sci. USA 2003, 100, 10592–10597. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ali, S.A.; Huang, M.B.; Campbell, P.E.; Roth, W.W.; Campbell, T.; Khan, M.; Newman, G.; Villinger, F.; Powell, M.D.; Bond, V.C. Genetic characterization of HIV type 1 Nef-induced vesicle secretion. AIDS Res. Hum. Retroviruses 2010, 26, 173–192. [Google Scholar] [CrossRef] [PubMed]
- Campbell, T.D.; Khan, M.; Huang, M.B.; Bond, V.C.; Powell, M.D. HIV-1 Nef protein is secreted into vesicles that can fuse with target cells and virions. Ethn. Dis. 2008, 18, S2-14-19. [Google Scholar] [PubMed]
- Sami Saribas, A.; Cicalese, S.; Ahooyi, T.M.; Khalili, K.; Amini, S.; Sariyer, I.K. HIV-1 Nef is released in extracellular vesicles derived from astrocytes: Evidence for Nef-mediated neurotoxicity. Cell. Death. Dis. 2017, 8, e2542. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Welsch, S.; Keppler, O.T.; Habermann, A.; Allespach, I.; Krijnse-Locker, J.; Krausslich, H.G. HIV-1 buds predominantly at the plasma membrane of primary human macrophages. PLoS Pathog. 2007, 3, e36. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Blanchard, E.; Belouzard, S.; Goueslain, L.; Wakita, T.; Dubuisson, J.; Wychowski, C.; Rouille, Y. Hepatitis C virus entry depends on clathrin-mediated endocytosis. J. Virol. 2006, 80, 6964–6972. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Meng, B.; Ip, N.C.; Prestwood, L.J.; Abbink, T.E.; Lever, A.M. Evidence that the endosomal sorting complex required for transport-II (ESCRT-II) is required for efficient human immunodeficiency virus-1 (HIV-1) production. Retrovirology 2015, 12, 72. [Google Scholar] [CrossRef] [Green Version]
- Bruce, E.A.; Digard, P.; Stuart, A.D. The Rab11 pathway is required for influenza A virus budding and filament formation. J. Virol. 2010, 84, 5848–5859. [Google Scholar] [CrossRef] [Green Version]
- Zou, X.; Gu, D.; Xing, X.; Cheng, Z.; Gong, D.; Zhang, G.; Zhu, Y. Human mesenchymal stromal cell-derived extracellular vesicles alleviate renal ischemic reperfusion injury and enhance angiogenesis in rats. Am. J. Transl. Res. 2016, 8, 4289–4299. [Google Scholar]
- Zou, L.; Ma, X.; Lin, S.; Wu, B.; Chen, Y.; Peng, C. Bone marrow mesenchymal stem cell-derived exosomes protect against myocardial infarction by promoting autophagy. Exp. Ther. Med. 2019, 18, 2574–2582. [Google Scholar] [CrossRef] [Green Version]
- Chen, T.S.; Lai, R.C.; Lee, M.M.; Choo, A.B.; Lee, C.N.; Lim, S.K. Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs. Nucleic Acids. Res. 2010, 38, 215–224. [Google Scholar] [CrossRef] [Green Version]
- Lai, R.C.; Tan, S.S.; Teh, B.J.; Sze, S.K.; Arslan, F.; de Kleijn, D.P.; Choo, A.; Lim, S.K. Proteolytic Potential of the MSC Exosome Proteome: Implications for an Exosome-Mediated Delivery of Therapeutic Proteasome. Int. J. Proteomics 2012, 2012, 971907. [Google Scholar] [CrossRef] [Green Version]
- Bari, E.; Ferrarotti, I.; Saracino, L.; Perteghella, S.; Torre, M.L.; Corsico, A.G. Mesenchymal Stromal Cell Secretome for Severe COVID-19 Infections: Premises for the Therapeutic Use. Cells 2020, 9, 924. [Google Scholar] [CrossRef] [Green Version]
- Sengupta, V.; Sengupta, S.; Lazo, A.; Woods, P.; Nolan, A.; Bremer, N. Exosomes Derived from Bone Marrow Mesenchymal Stem Cells as Treatment for Severe COVID-19. Stem Cells Dev. 2020, 29, 747–754. [Google Scholar] [CrossRef]
- Lim, S.K.; Giebel, B.; Weiss, D.J.; Witwer, K.W.; Rohde, E. Re: “Exosomes Derived from Bone Marrow Mesenchymal Stem Cells as Treatment for Severe COVID-19” by Sengupta et al. Stem Cells Dev. 2020. [Google Scholar] [CrossRef]
- Chong, S.Y.; Lee, C.K.; Huang, C.; Ou, Y.H.; Charles, C.J.; Richards, A.M.; Neupane, Y.R.; Pavon, M.V.; Zharkova, O.; Pastorin, G.; et al. Extracellular vesicles in cardiovascular diseases: Alternative biomarker sources, therapeutic agents, and drug delivery carriers. Int. J. Mol. Sci. 2019, 20, 3272. [Google Scholar] [CrossRef] [Green Version]
- Loyer, X.; Zlatanova, I.; Devue, C.; Yin, M.; Howangyin, K.Y.; Klaihmon, P.; Guerin, C.L.; Kheloufi, M.; Vilar, J.; Zannis, K.; et al. Intra-Cardiac Release of Extracellular Vesicles Shapes Inflammation Following Myocardial Infarction. Circ. Res. 2018, 123, 100–106. [Google Scholar] [CrossRef]
- Ribeiro-Rodrigues, T.M.; Laundos, T.L.; Pereira-Carvalho, R.; Batista-Almeida, D.; Pereira, R.; Coelho-Santos, V.; Silva, A.P.; Fernandes, R.; Zuzarte, M.; Enguita, F.J.; et al. Exosomes secreted by cardiomyocytes subjected to ischaemia promote cardiac angiogenesis. Cardiovasc. Res. 2017, 113, 1338–1350. [Google Scholar] [CrossRef] [Green Version]
- New, S.E.; Aikawa, E. Role of extracellular vesicles in de novo mineralization: An additional novel mechanism of cardiovascular calcification. Arterioscler. Thromb. Vasc. Biol. 2013, 33, 1753–1758. [Google Scholar] [CrossRef] [Green Version]
- Pokhrel, R.; Gerstman, B.S.; Hutcheson, J.D.; Chapagain, P.P. In Silico Investigations of Calcium Phosphate Mineralization in Extracellular Vesicles. J. Phys. Chem. B 2018, 122, 3782–3789. [Google Scholar] [CrossRef]
- Hutcheson, J.D.; Goettsch, C.; Pham, T.; Iwashita, M.; Aikawa, M.; Singh, S.A.; Aikawa, E. Enrichment of calcifying extracellular vesicles using density-based ultracentrifugation protocol. J. Extracell. Vesicles 2014, 3, 1–12. [Google Scholar] [CrossRef]
- Kapustin, A.N.; Davies, J.D.; Reynolds, J.L.; McNair, R.; Jones, G.T.; Sidibe, A.; Schurgers, L.J.; Skepper, J.N.; Proudfoot, D.; Mayr, M.; et al. Calcium regulates key components of vascular smooth muscle cell-derived matrix vesicles to enhance mineralization. Circ. Res. 2011, 109, e1–e12. [Google Scholar] [CrossRef] [Green Version]
- Goettsch, C.; Hutcheson, J.D.; Aikawa, M.; Iwata, H.; Pham, T.; Nykjaer, A.; Kjolby, M.; Rogers, M.; Michel, T.; Shibasaki, M.; et al. Sortilin mediates vascular calcification via its recruitment into extracellular vesicles. J. Clin. Investig. 2016, 126, 1323–1336. [Google Scholar] [CrossRef]
- Genge, B.R.; Wu, L.N.; Wuthier, R.E. In vitro modeling of matrix vesicle nucleation: Synergistic stimulation of mineral formation by annexin A5 and phosphatidylserine. J. Biol. Chem. 2007, 282, 26035–26045. [Google Scholar] [CrossRef] [Green Version]
- Chen, N.X.; O’Neill, K.D.; Chen, X.; Moe, S.M. Annexin-mediated matrix vesicle calcification in vascular smooth muscle cells. J. Bone Miner. Res. 2008, 23, 1798–1805. [Google Scholar] [CrossRef] [Green Version]
- New, S.E.; Goettsch, C.; Aikawa, M.; Marchini, J.F.; Shibasaki, M.; Yabusaki, K.; Libby, P.; Shanahan, C.M.; Croce, K.; Aikawa, E. Macrophage-derived matrix vesicles: An alternative novel mechanism for microcalcification in atherosclerotic plaques. Circ. Res. 2013, 113, 72–77. [Google Scholar] [CrossRef]
- Deng, L.; Peng, Y.; Jiang, Y.; Wu, Y.; Ding, Y.; Wang, Y.; Xu, D.; Fu, Q. Imipramine protects against bone loss by inhibition of osteoblast-derived microvesicles. Int. J. Mol. Sci. 2017, 18, 1013. [Google Scholar] [CrossRef] [Green Version]
- Komatsu, M.; Waguri, S.; Chiba, T.; Murata, S.; Iwata, J.; Tanida, I.; Ueno, T.; Koike, M.; Uchiyama, Y.; Kominami, E.; et al. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 2006, 441, 880–884. [Google Scholar] [CrossRef] [PubMed]
- Fussi, N.; Hollerhage, M.; Chakroun, T.; Nykanen, N.P.; Rosler, T.W.; Koeglsperger, T.; Wurst, W.; Behrends, C.; Hoglinger, G.U. Exosomal secretion of alpha-synuclein as protective mechanism after upstream blockage of macroautophagy. Cell Death Dis. 2018, 9, 757. [Google Scholar] [CrossRef] [Green Version]
- Asai, H.; Ikezu, S.; Tsunoda, S.; Medalla, M.; Luebke, J.; Haydar, T.; Wolozin, B.; Butovsky, O.; Kugler, S.; Ikezu, T. Depletion of microglia and inhibition of exosome synthesis halt tau propagation. Nat. Neurosci. 2015, 18, 1584–1593. [Google Scholar] [CrossRef]
- Lee, J.A.; Beigneux, A.; Ahmad, S.T.; Young, S.G.; Gao, F.B. ESCRT-III dysfunction causes autophagosome accumulation and neurodegeneration. Curr. Biol. 2007, 17, 1561–1567. [Google Scholar] [CrossRef] [Green Version]
- Payrastre, B.; Missy, K.; Giuriato, S.; Bodin, S.; Plantavid, M.; Gratacap, M. Phosphoinositides: Key players in cell signalling, in time and space. Cell. Signal. 2001, 13, 377–387. [Google Scholar] [CrossRef]
- Janmey, P.A.; Lindberg, U. Cytoskeletal regulation: Rich in lipids. Nat. Rev. Mol. Cell. Biol. 2004, 5, 658–666. [Google Scholar] [CrossRef]
- De Craene, J.O.; Bertazzi, D.L.; Bar, S.; Friant, S. Phosphoinositides, Major Actors in Membrane Trafficking and Lipid Signaling Pathways. Int. J. Mol. Sci. 2017, 18, 634. [Google Scholar] [CrossRef]
- Audhya, A.; Foti, M.; Emr, S.D. Distinct roles for the yeast phosphatidylinositol 4-kinases, Stt4p and Pik1p, in secretion, cell growth, and organelle membrane dynamics. Mol. Biol. Cell 2000, 11, 2673–2689. [Google Scholar] [CrossRef] [Green Version]
- Kihara, A.; Noda, T.; Ishihara, N.; Ohsumi, Y. Two distinct Vps34 phosphatidylinositol 3-kinase complexes function in autophagy and carboxypeptidase Y sorting in Saccharomyces cerevisiae. J. Cell. Biol. 2001, 152, 519–530. [Google Scholar] [CrossRef] [Green Version]
- Obara, K.; Ohsumi, Y. PtdIns 3-Kinase Orchestrates Autophagosome Formation in Yeast. J. Lipids 2011, 2011, 498768. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gruenberg, J.; Stenmark, H. The biogenesis of multivesicular endosomes. Nat. Rev. Mol. Cell. Biol. 2004, 5, 317–323. [Google Scholar] [CrossRef]
- van Weering, J.R.; Verkade, P.; Cullen, P.J. SNX-BAR proteins in phosphoinositide-mediated, tubular-based endosomal sorting. Semin. Cell. Dev. Biol. 2010, 21, 371–380. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Boal, F.; Mansour, R.; Gayral, M.; Saland, E.; Chicanne, G.; Xuereb, J.M.; Marcellin, M.; Burlet-Schiltz, O.; Sansonetti, P.J.; Payrastre, B.; et al. TOM1 is a PI5P effector involved in the regulation of endosomal maturation. J. Cell. Sci. 2015, 128, 815–827. [Google Scholar] [CrossRef] [Green Version]
- Ferguson, C.J.; Lenk, G.M.; Meisler, M.H. Defective autophagy in neurons and astrocytes from mice deficient in PI(3,5)P2. Hum. Mol. Genet. 2009, 18, 4868–4878. [Google Scholar] [CrossRef] [Green Version]
- Cao, Q.; Yang, Y.; Zhong, X.Z.; Dong, X.P. The lysosomal Ca2+ release channel TRPML1 regulates lysosome size by activating calmodulin. J. Biol. Chem. 2017, 292, 8424–8435. [Google Scholar] [CrossRef] [Green Version]
- Hong, N.H.; Qi, A.; Weaver, A.M. PI(3,5)P2 controls endosomal branched actin dynamics by regulating cortactin-Actin interactions. J. Cell Biol. 2015, 210, 753–769. [Google Scholar] [CrossRef]
- Whitley, P.; Reaves, B.J.; Hashimoto, M.; Riley, A.M.; Potter, B.V.; Holman, G.D. Identification of mammalian Vps24p as an effector of phosphatidylinositol 3,5-bisphosphate-dependent endosome compartmentalization. J. Biol. Chem. 2003, 278, 38786–38795. [Google Scholar] [CrossRef] [Green Version]
- Essandoh, K.; Yang, L.; Wang, X.; Huang, W.; Qin, D.; Hao, J.; Wang, Y.; Zingarelli, B.; Peng, T.; Fan, G.C. Blockade of exosome generation with GW4869 dampens the sepsis-induced inflammation and cardiac dysfunction. Biochim. Biophys. Acta 2015, 1852, 2362–2371. [Google Scholar] [CrossRef] [Green Version]
- Guo, B.B.; Bellingham, S.A.; Hill, A.F. Stimulating the release of exosomes increases the intercellular transfer of prions. J. Biol. Chem. 2016, 291, 5128–5137. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, J.; Yeung, B.Z.; Cui, M.; Peer, C.J.; Lu, Z.; Figg, W.D.; Guillaume Wientjes, M.; Woo, S.; Au, J.L. Exosome is a mechanism of intercellular drug transfer: Application of quantitative pharmacology. J. Control Release 2017, 268, 147–158. [Google Scholar] [CrossRef]
- Hatzidaki, E.; Vlachou, I.; Elka, A.; Georgiou, E.; Papadimitriou, M.; Iliopoulos, A.; Papasotiriou, I. The use of serum extracellular vesicles for novel small molecule inhibitor cell delivery. Anticancer Drugs 2019, 30, 271–280. [Google Scholar] [CrossRef]
- Kim, M.S.; Haney, M.J.; Zhao, Y.; Mahajan, V.; Deygen, I.; Klyachko, N.L.; Inskoe, E.; Piroyan, A.; Sokolsky, M.; Okolie, O.; et al. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine 2016, 12, 655–664. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Haney, M.J.; Klyachko, N.L.; Zhao, Y.; Gupta, R.; Plotnikova, E.G.; He, Z.; Patel, T.; Piroyan, A.; Sokolsky, M.; Kabanov, A.V.; et al. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J. Control Release 2015, 207, 18–30. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Alvarez-Erviti, L.; Seow, Y.; Yin, H.; Betts, C.; Lakhal, S.; Wood, M.J. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat. Biotechnol. 2011, 29, 341–345. [Google Scholar] [CrossRef]
- Melling, G.E.; Carollo, E.; Conlon, R.; Simpson, J.C.; Carter, D.R.F. The Challenges and Possibilities of Extracellular Vesicles as Therapeutic Vehicles. Eur. J. Pharm. Biopharm. 2019, 144, 50–56. [Google Scholar] [CrossRef]
- Domotor, E.; Abbott, N.J.; Adam-Vizi, V. Na+-Ca2+ exchange and its implications for calcium homeostasis in primary cultured rat brain microvascular endothelial cells. J. Physiol. 1999, 515, 147–155. [Google Scholar] [CrossRef] [PubMed]
- Savina, A.; Furlán, M.; Vidal, M.; Colombo, M.I. Exosome release is regulated by a calcium-dependent mechanism in K562 cells. J. Biol. Chem. 2003, 278, 20083–20090. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gangoda, L.; Mathivanan, S. Cortactin enhances exosome secretion without altering cargo. J. Cell Biol. 2016, 214, 129–131. [Google Scholar] [CrossRef] [Green Version]
- Ibrahim, A.G.; Cheng, K.; Marban, E. Exosomes as critical agents of cardiac regeneration triggered by cell therapy. Stem Cell Reports 2014, 2, 606–619. [Google Scholar] [CrossRef] [Green Version]
- Arenz, C.; Thutewohl, M.; Block, O.; Waldmann, H.; Altenbach, H.J.; Giannis, A. Manumycin A and its analogues are irreversible inhibitors of neutral sphingomyelinase. Chembiochem 2001, 2, 141–143. [Google Scholar] [CrossRef]
- Sexton, R.E.; Mpilla, G.; Kim, S.; Philip, P.A.; Azmi, A.S. Ras and exosome signaling. Semin. Cancer Biol. 2019, 54, 131–137. [Google Scholar] [CrossRef]
- Phuyal, S.; Hessvik, N.P.; Skotland, T.; Sandvig, K.; Llorente, A. Regulation of exosome release by glycosphingolipids and flotillins. FEBS J. 2014, 281, 2214–2227. [Google Scholar] [CrossRef] [PubMed]
- Hofmann, K.; Tomiuk, S.; Wolff, G.; Stoffel, W. Cloning and characterization of the mammalian brain-specific, Mg2+-dependent neutral sphingomyelinase. Proc. Natl. Acad. Sci. USA 2000, 97, 5895–5900. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Khan, S.; Jutzy, J.M.S.; Aspe, J.R.; McGregor, D.W.; Neidigh, J.W.; Wall, N.R. Survivin is released from cancer cells via exosomes. Apoptosis 2011, 16, 1–12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Miyoshi, H.; Umeshita, K.; Sakon, M.; Imajoh-Ohmi, S.; Fujitani, K.; Gotoh, M.; Oiki, E.; Kambayashi, J.; Monden, M. Calpain activation in plasma membrane bleb formation during tert-butyl hydroperoxide-induced rat hepatocyte injury. Gastroenterology 1996, 110, 1897–1904. [Google Scholar] [CrossRef] [PubMed]
- Abid Hussein, M.N.; Boing, A.N.; Sturk, A.; Hau, C.M.; Nieuwland, R. Inhibition of microparticle release triggers endothelial cell apoptosis and detachment. Thromb. Haemost. 2007, 98, 1096–1107. [Google Scholar] [CrossRef] [Green Version]
- Hessvik, N.P.; Øverbye, A.; Brech, A.; Torgersen, M.L.; Jakobsen, I.S.; Sandvig, K.; Llorente, A. PIKfyve inhibition increases exosome release and induces secretory autophagy. Cell. Mol. Life Sci. 2016, 73, 4717–4737. [Google Scholar] [CrossRef]
Cargo Sorting Machinery | Reported Cargo | References |
---|---|---|
ESCRT-complex | proteins (ubiquitin-tagged) | [34] |
Ubiquitin Binding Proteins (ISG15, UBL3) | proteins (ubiquitin-tagged) | [35,36] |
Alix (ESCRT-III associated) | proteins (especially receptors; ubiquitin-independent) | [37] |
Alix-Syntenin-Syndecan-complex (Phospholipase D2–ARF6-regulated) | proteins (binding to heparanase sulfate) | [38] |
Ndfip1 | proteins (Nedd4 family members or WW-tagged) | [39,40] |
sphingosine-1-phosphate and receptor | proteins (transferrin receptor, CD63) | [41] |
Tetraspannins (CD9, CD63) | proteins (specifically interacting) | [42,43] |
ARRDC1–Vps4/TSG101 | proteins (microparticle exclusive) | [44] |
lipid raft associated sorting | proteins | [45,46] |
sumoylated hnRNPA2B1 (ceramide regulated) | miRNA (EXOmotif) | [47] |
sumoylated SYNCRIP | miRNA | [48] |
Alix–Ago2 | miRNA | [49] |
KRAS | miRNA | [50] |
YBX1 | miRNA | [51] |
HuR | miRNA | [52] |
Lc3b-machinery (associated to RNA binding proteins) | non-coding RNA | [53] |
unknown | mtDNA | [54] |
unknown | mineral | [55,56] |
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Mir, B.; Goettsch, C. Extracellular Vesicles as Delivery Vehicles of Specific Cellular Cargo. Cells 2020, 9, 1601. https://doi.org/10.3390/cells9071601
Mir B, Goettsch C. Extracellular Vesicles as Delivery Vehicles of Specific Cellular Cargo. Cells. 2020; 9(7):1601. https://doi.org/10.3390/cells9071601
Chicago/Turabian StyleMir, Bilal, and Claudia Goettsch. 2020. "Extracellular Vesicles as Delivery Vehicles of Specific Cellular Cargo" Cells 9, no. 7: 1601. https://doi.org/10.3390/cells9071601
APA StyleMir, B., & Goettsch, C. (2020). Extracellular Vesicles as Delivery Vehicles of Specific Cellular Cargo. Cells, 9(7), 1601. https://doi.org/10.3390/cells9071601