Logan, Curtis John (2022) Humanization of Yeast Exosome Protein Selection Machinery to Investigate Functional Evolutionary Conservation. Masters thesis, Concordia University.
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Abstract
Extracellular vesicles (EVs) mediate intercellular communication underlying diverse (patho)physiology, including responses to stress, in all organisms studied from bacteria to yeast to human. However, relatively little is understood about the molecular machinery underpinning fundamental EV biology. The Endosomal Sorting Complex Required for Transport (ESCRT) pathway contributes to the biogenesis of small EV populations called exosomes, including selective loading of luminal and membrane protein cargo. Our group discovered that EVs produced by baker’s yeast (Saccharomyces cerevisiae) confer thermotolerance. Herein, my aim is to use this powerful model organism to study functional evolutionary conservation of ESCRT–mediated exosome biogenesis. I replaced yeast VPS23 (yeast vacuolar sorting protein 23), a component of ESCRT-I critical for protein cargo selection, with its human orthologue TSG101, a conventional EV biomarker, tagged it to GFP and evaluated if it confers EV cargo loading, biogenesis and bioactivity. After confirming TSG101-GFP protein expression in yeast by Western blot analysis and fluorescence microscopy, I collected EVs and measured their size by Nanoparticle Tracking Analysis (NTA), total protein content by Bradford assay, and GFP-fluorescence using fluorimetry. EVs were also visualized using transmission electron microscopy to assess structural morphology and confirm size. To assess the capacity to restore bioactivity, I collected EVs from conditioned yeast and measured their ability to provide thermotolerance to naïve cells using a methylene blue- based viability assay and light microscopy. Proteomic analysis by mass spectrometry was conducted to identify EV proteins. In all, I found that human Tsg101-GFP seems to localize at sites of exosome biosynthesis within cells, is present in EVs, and replaces most yeast Vps23 functions in exosome biogenesis, suggesting deep evolutionary conservation of ESCRT–mediated EV biology. These studies set the stage for research focused on better understanding the basis of selective protein cargo loading using S. cerevisiae as a model.
| Divisions: | Concordia University > Faculty of Arts and Science > Biology |
|---|---|
| Item Type: | Thesis (Masters) |
| Authors: | Logan, Curtis John |
| Institution: | Concordia University |
| Degree Name: | M. Sc. |
| Program: | Biology |
| Date: | 5 December 2022 |
| Thesis Supervisor(s): | Brett, Christopher, L |
| ID Code: | 991753 |
| Deposited By: | Curtis Logan |
| Deposited On: | 21 Jun 2023 14:50 |
| Last Modified: | 21 Jun 2023 14:50 |
References:
Akers JC, Gonda D, Kim R, Carter BS, Chen CC. Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J Neurooncol. 2013 May;113(1):1-11. doi: 10.1007/s11060-013-1084-8.Babst M, Odorizzi G, Estepa EJ, Emr SD. Mammalian tumor susceptibility gene 101 (TSG101) and the yeast homologue, Vps23p, both function in late endosomal trafficking. Traffic. 2000 Mar;1(3):248-58. doi: 10.1034/j.1600-0854.2000.010307.x.
Bagnat M, Keränen S, Shevchenko A, Shevchenko A, Simons K. Lipid rafts function in biosynthetic delivery of proteins to the cell surface in yeast. Proc Natl Acad Sci U S A. 2000 Mar 28;97(7):3254-9. doi: 10.1073/pnas.97.7.3254.
Baietti MF, Zhang Z, Mortier E, Melchior A, Degeest G, Geeraerts A, Ivarsson Y, Depoortere F, Coomans C, Vermeiren E, Zimmermann P, David G. 2012. Syndecan-syntenin-ALIX regulates the biogenesis of exosomes. Nat Cell Biol.3;14(7):677-85. doi: 10.1038/ncb2502.
Bari, R., Guo, Q., Xia, V., Zhang, YH., Giesert, EE., Levy, S, et al. (2011) Tetraspanins regulate the protrusive activities of cell membrane. Biochem Biophys Res Commun. 415(4):619-26. doi:10.1016/j.bbrc.2011.10.121
Battistelli M, Falcieri E. 2020. Apoptotic Bodies: Particular Extracellular Vesicles Involved in Intercellular Communication. Biology (Basel). 20;9(1):21. doi: 10.3390/biology9010021
Beit-Yannai E, Tabak S, Stamer WD. Physical exosome:exosome interactions. J Cell Mol Med. 2018 Mar;22(3):2001-2006. doi: 10.1111/jcmm.13479.
Bellingham SA, Guo BB, Coleman BM, Hill AF. Exosomes: vehicles for the transfer of toxic proteins associated with neurodegenerative diseases? Front Physiol. 2012 May 3;3:124. doi: 10.3389/fphys.2012.00124.
Bishop N, Woodman P. TSG101/mammalian VPS23 and mammalian VPS28 interact directly and are recruited to VPS4-induced endosomes. J Biol Chem. 2001 Apr 13;276(15):11735-42. doi: 10.1074/jbc.M009863200.
Bishop N, Horman A, Woodman P. Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal protein-ubiquitin conjugates. J Cell Biol. 2002 Apr 1;157(1):91-101. doi: 10.1083/jcb.200112080.
Blanco S, Lazo PA. 2003. Human TSG101 does not replace Saccharomyces cerevisiae VPS23 role in the quality control of plasma membrane proteins. FEMS Microbiol Lett. 25;221(2):151-4. doi: 10.1016/S0378-1097(03)00179-4.
Böker KO, Lemus-Diaz N, Rinaldi Ferreira R, Schiller L, Schneider S, Gruber J. 2018. The Impact of the CD9 Tetraspanin on Lentivirus Infectivity and Exosome Secretion. Mol Ther. Feb 7;26(2):634-647. doi: 10.1016/j.ymthe.2017.11.008.
Borges F., Reis L., Schor N. 2013. Extracellular vesicles: Structure, function, and potential clinical uses in renal diseases. Braz. J. Med. Biol. Res. 46:824–830. doi: 10.1590/1414-431X20132964.
Bose S, Aggarwal S, Singh DV, Acharya N. 2020. Extracellular vesicles: An emerging platform in gram-positive bacteria. Microb Cell.5;7(12):312-322. doi: 10.15698/mic2020.12.737.
Brinton LT, Sloane HS, Kester M, Kelly KA. Formation and role of exosomes in cancer. Cell Mol Life Sci. 2015 Feb;72(4):659-71. doi: 10.1007/s00018-014-1764-3
Cai J, Wu J, Wang J, Li Y, Hu X, Luo S, Xiang D. Extracellular vesicles derived from different sources of mesenchymal stem cells: therapeutic effects and translational potential. Cell Biosci. 2020 May 24;10:69. doi: 10.1186/s13578-020-00427-x.
Buschow SI, Liefhebber JM, Wubbolts R, Stoorvogel W. Exosomes contain ubiquitinated proteins. Blood Cells Mol Dis. 2005 Nov-Dec;35(3):398-403. doi: 10.1016/j.bcmd.2005.08.005.
Caruso S, Atkin-Smith GK, Baxter AA, Tixeira R, Jiang L, Ozkocak DC, Santavanond JP, Hulett MD, Lock P, Phan TK, Poon IKH. Defining the role of cytoskeletal components in the formation of apoptopodia and apoptotic bodies during apoptosis. Apoptosis. 2019 Dec;24(11-12):862-877. doi: 10.1007/s10495-019-01565-5.
Caruso S, Poon IKH. Apoptotic Cell-Derived Extracellular Vesicles: More Than Just Debris. Front Immunol. 2018 Jun 28;9:1486. doi: 10.3389/fimmu.2018.01486.
Chronopoulos A, Kalluri R. Emerging role of bacterial extracellular vesicles in cancer. Oncogene. 2020 Nov;39(46):6951-6960. doi: 10.1038/s41388-020-01509-3.
Chu T, Sun J, Saksena S, Emr SD. New component of ESCRT-I regulates endosomal sorting complex assembly. J Cell Biol. 2006 Dec 4;175(5):815-23. doi: 10.1083/jcb.200608053.
Chua HH, Lee HH, Chang SS, Lu CC, Yeh TH, Hsu TY, Cheng TH, Cheng JT, Chen MR, Tsai CH. 2006. Role of the TSG101 gene in Epstein-Barr virus late gene transcription. J Virol. 2007 Mar;81(5):2459-71. doi: 10.1128/JVI.02289-06.
Colombo M, Moita C, van Niel G, Kowal J, Vigneron J, Benaroch P, Manel N, Moita LF, Théry C, Raposo G. 2013.Analysis of ESCRT functions in exosome biogenesis, composition and secretion highlights the heterogeneity of extracellular vesicles. J Cell Sci. 2013 Dec 15;126(Pt 24):5553-65. doi: 10.1242/jcs.128868
Conde-Vancells J, Rodriguez-Suarez E, Embade N, Gil D, Matthiesen R, Valle M, Elortza F, Lu SC, Mato JM, Falcon-Perez JM. Characterization and comprehensive proteome profiling of exosomes secreted by hepatocytes. J Proteome Res. 2008 Dec;7(12):5157-66. doi: 10.1021/pr8004887.
Curtiss M, Jones C, Babst M. Efficient cargo sorting by ESCRT-I and the subsequent release of ESCRT-I from multivesicular bodies requires the subunit Mvb12. Mol Biol Cell. 2007 Feb;18(2):636-45. doi:10.1091/mbc.e06-07-0588.
Dawaliby R, Trubbia C, Delporte C, Noyon C, Ruysschaert JM, Van Antwerpen P, Govaerts C. Phosphatidylethanolamine Is a Key Regulator of Membrane Fluidity in Eukaryotic Cells. J Biol Chem. 2016 Feb 12;291(7):3658-67. doi: 10.1074/jbc.M115.706523.
Dawson CS, Garcia-Ceron D, Rajapaksha H, Faou P, Bleackley MR, Anderson MA. Protein markers for Candida albicans EVs include claudin-like Sur7 family proteins. J Extracell Vesicles. 2020 Apr 16;9(1):1750810. doi: 10.1080/20013078.2020.1750810
Dolnik O, Kolesnikova L, Welsch S, Strecker T, Schudt G, Becker S. 2014. Interaction with Tsg101 is necessary for the efficient transport and release of nucleocapsids in marburg virus-infected cells. PLoS Pathog. 2014 Oct 16;10(10):e1004463. doi: 10.1371/journal.ppat.1004463.
Donoso-Quezada J, Ayala-Mar S, González-Valdez J. The role of lipids in exosome biology and intercellular communication: Function, analytics and applications. Traffic. 2021 Jul;22(7):204-220. doi: 10.1111/tra.12803.
Dou G, Tian R, Liu X, Yuan P, Ye Q, Liu J, Liu S, Zhou J, Deng Z, Chen X, Liu S, Jin Y. Chimeric apoptotic bodies functionalized with natural membrane and modular delivery system for inflammation modulation. Sci Adv. 2020 Jul 22;6(30):eaba2987. doi:10.1126/sciadv.aba2987.
Doyle LM, Wang MZ. 2019. Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells. 2019 Jul 15;8(7):727. doi: 10.3390/cells8070727.
Edgar JR. Q&A: What are exosomes, exactly? BMC Biol. 2016 Jun 13;14:46. doi: 10.1186/s12915-016-0268-z.
Eldh M, Ekström K, Valadi H, Sjöstrand M, Olsson B, Jernås M, Lötvall J. Exosomes communicate protective messages during oxidative stress; possible role of exosomal shuttle RNA. PLoS One. 2010 Dec 17;5(12):e15353. doi: 10.1371/journal.pone.0015353.
Elsherbini A, Qin H, Zhu Z, Tripathi P, Wang G, Crivelli SM, Spassieva SD, Bieberich E. Extracellular Vesicles Containing Ceramide-Rich Platforms: "Mobile Raft" Isolation and Analysis. Methods Mol Biol. 2021;2187:87-98. doi: 10.1007/978-1-0716-0814-2_5.
Galao RP, Scheller N, Alves-Rodrigues I, Breinig T, Meyerhans A, Díez J. Saccharomyces cerevisiae: a versatile eukaryotic system in virology. Microb Cell Fact. 2007 Oct 10;6:32. doi: 10.1186/1475-2859-6-32.
Galleu A, Riffo-Vasquez Y, Trento C, Lomas C, Dolcetti L, Cheung TS, von Bonin M, Barbieri L, Halai K, Ward S, Weng L, Chakraverty R, Lombardi G, Watt FM, Orchard K, Marks DI, Apperley J, Bornhauser M, Walczak H, Bennett C, Dazzi F. Apoptosis in mesenchymal stromal cells induces in vivo recipient-mediated immunomodulation. Sci Transl Med. 2017 Nov 15;9(416):eaam7828. doi: 10.1126/scitranslmed.aam7828
Garrus JE, von Schwedler UK, Pornillos OW, Morham SG, Zavitz KH, Wang HE, Wettstein DA, Stray KM, Côté M, Rich RL, Myszka DG, Sundquist WI. 2001.Tsg101 and the vacuolar protein sorting pathway are essential for HIV-1 budding. Cell. 5;107(1):55-65. doi: 10.1016/s0092-8674(01)00506-2.
Gebara, N., Rossi, A., Skovronova, R. et al. 2020. Extracellular Vesicles, Apoptotic Bodies and Mitochondria: Stem Cell Bioproducts for Organ Regeneration. Curr Transpl Rep 7, 105–113. doi.org/10.1007/s40472-020-00282-2
Gebremedhn S, Gad A, Aglan HS, Laurincik J, Prochazka R, Salilew-Wondim D, Hoelker M, Schellander K, Tesfaye D. Extracellular vesicles shuttle protective messages against heat stress in bovine granulosa cells. Sci Rep. 2020 Sep 25;10(1):15824. doi: 10.1038/s41598-020-72706-z.
Gill DJ, Teo H, Sun J, Perisic O, Veprintsev DB, Emr SD, Williams RL. Structural insight into the ESCRT-I/-II link and its role in MVB trafficking. EMBO J. 2007 Jan 24;26(2):600-12. doi: 10.1038/sj.emboj.7601501.
Gill S, Catchpole R, Forterre P. Extracellular membrane vesicles in the three domains of life and beyond. FEMS Microbiol Rev. 2019 May 1;43(3):273-303. doi: 10.1093/femsre/fuy042.
Giordano C, Gelsomino L, Barone I, Panza S, Augimeri G, Bonofiglio D, Rovito D, Naimo GD, Leggio A, Catalano S, Andò S. Leptin Modulates Exosome Biogenesis in Breast Cancer Cells: An Additional Mechanism in Cell-to-Cell Communication. J Clin Med. 2019 Jul 12;8(7):1027. doi: 10.3390/jcm8071027.
Guan XL, Souza CM, Pichler H, Dewhurst G, Schaad O, Kajiwara K, Wakabayashi H, Ivanova T, Castillon GA, Piccolis M, Abe F, Loewith R, Funato K, Wenk MR, Riezman H. Functional interactions between sphingolipids and sterols in biological membranes regulating cell physiology. Mol Biol Cell. 2009 Apr;20(7):2083-95. doi: 10.1091/mbc.e08-11-1126.
Gutiérrez-Vázquez C, Villarroya-Beltri C, Mittelbrunn M, Sánchez-Madrid F. Transfer of extracellular vesicles during immune cell-cell interactions. Immunol Rev. 2013 Jan;251(1):125-42. doi: 10.1111/imr.12013.
Grant BD, Donaldson JG. Pathways and mechanisms of endocytic recycling. Nat Rev Mol Cell Biol. 2009;10:597–608. doi: 10.1038/nrm2755.
Han QF, Li WJ, Hu KS, Gao J, Zhai WL, Yang JH, Zhang SJ. Exosome biogenesis: machinery, regulation, and therapeutic implications in cancer. Mol Cancer. 2022 Nov 1;21(1):207. doi: 10.1186/s12943-022-01671-0.
Hanson PI, Cashikar A. Multivesicular body morphogenesis. Annu Rev Cell Dev Biol. 2012;28:337-62. doi: 10.1146/annurev-cellbio-092910-154152.
Hauser P, Wang S, Didenko VV. Apoptotic Bodies: Selective Detection in Extracellular Vesicles. Methods Mol Biol. 2017;1554:193-200. doi: 10.1007/978-1-4939-6759-9_12.
Heijnen HF, Schiel AE, Fijnheer R, Geuze HJ, Sixma JJ. Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. Blood. 1999 Dec 1;94(11):3791-9.
Henne WM, Stenmark H, Emr SD. Molecular mechanisms of the membrane sculpting ESCRT pathway. Cold Spring Harb Perspect Biol. 2013 Sep 1;5(9):a016766. doi:10.1101/cshperspect.a016766.
Horbay R, Hamraghani A, Ermini L, Holcik S, Beug ST, Yeganeh B. Role of Ceramides and Lysosomes in Extracellular Vesicle Biogenesis, Cargo Sorting and Release. Int J Mol Sci. 2022 Dec 5;23(23):15317. doi: 10.3390/ijms232315317.
Hoshino A, Kim HS, Bojmar L, Gyan KE, Cioffi M, Hernandez J, Zambirinis CP, Rodrigues G, Molina H, Heissel S, Mark MT, Steiner L, Benito-Martin A, Lucotti S, Di Giannatale A, Offer K, Nakajima M, Williams C, Nogués L, Pelissier Vatter FA, Hashimoto A, Davies AE, Freitas D, Kenific CM, Ararso Y, Buehring W, Lauritzen P, Ogitani Y, Sugiura K, Takahashi N, Alečković M, Bailey KA, Jolissant JS, Wang H, Harris A, Schaeffer LM, García-Santos G, Posner Z, Balachandran VP, Khakoo Y, Raju GP, Scherz A, Sagi I, Scherz-Shouval R, Yarden Y, Oren M, Malladi M, Petriccione M, De Braganca KC, Donzelli M, Fischer C, Vitolano S, Wright GP, Ganshaw L, Marrano M, Ahmed A, DeStefano J, Danzer E, Roehrl MHA, Lacayo NJ, Vincent TC, Weiser MR, Brady MS, Meyers PA, Wexler LH, Ambati SR, Chou AJ, Slotkin EK, Modak S, Roberts SS, Basu EM, Diolaiti D, Krantz BA, Cardoso F, Simpson AL, Berger M, Rudin CM, Simeone DM, Jain M, Ghajar CM, Batra SK, Stanger BZ, Bui J, Brown KA, Rajasekhar VK, Healey JH, de Sousa M, Kramer K, Sheth S, Baisch J, Pascual V, Heaton TE, La Quaglia MP, Pisapia DJ, Schwartz R, Zhang H, Liu Y, Shukla A, Blavier L, DeClerck YA, LaBarge M, Bissell MJ, Caffrey TC, Grandgenett PM, Hollingsworth MA, Bromberg J, Costa-Silva B, Peinado H, Kang Y, Garcia BA, O'Reilly EM, Kelsen D, Trippett TM, Jones DR, Matei IR, Jarnagin WR, Lyden D. Extracellular Vesicle and Particle Biomarkers Define Multiple Human Cancers. Cell. 2020 Aug 20;182(4):1044-1061.e18. doi: 10.1016/j.cell.2020.07.009.
Hristov M, Erl W, Linder S, Weber PC. Apoptotic bodies from endothelial cells enhance the number and initiate the differentiation of human endothelial progenitor cells in vitro. Blood. 2004;104(9):2761–6. doi: 10.1182/blood-2003-10-3614.
Hurst LR, Fratti RA. Lipid Rafts, Sphingolipids, and Ergosterol in Yeast Vacuole Fusion and Maturation. Front Cell Dev Biol. 2020 Jul 3;8:539. doi: 10.3389/fcell.2020.00539.
Jeppesen DK, Fenix AM, Franklin JL, Higginbotham JN, Zhang Q, Zimmerman LJ, Liebler DC, Ping J, Liu Q, Evans R, Fissell WH, Patton JG, Rome LH, Burnette DT, Coffey RJ. Reassessment of Exosome Composition. Cell. 2019 Apr 4;177(2):428-445.e18. doi: 10.1016/j.cell.2019.02.029.
Jiang L, Paone S, Caruso S, Atkin-Smith GK, Phan TK, Hulett MD, Poon IKH. Determining the contents and cell origins of apoptotic bodies by flow cytometry. Sci Rep. 2017 Oct 31;7(1):14444. doi: 10.1038/s41598-017-14305-z.
Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, Tunyasuvunakool K, Bates R, Žídek A, Potapenko A, Bridgland A, Meyer C, Kohl SAA, Ballard AJ, Cowie A, Romera-Paredes B, Nikolov S, Jain R, Adler J, Back T, Petersen S, Reiman D, Clancy E, Zielinski M, Steinegger M, Pacholska M, Berghammer T, Bodenstein S, Silver D, Vinyals O, Senior AW, Kavukcuoglu K, Kohli P, Hassabis D. Highly accurate protein structure prediction with AlphaFold. Nature. 2021 Aug;596(7873):583-589. doi: 10.1038/s41586-021-03819-2.
Karkowska-Kuleta J, Kulig K, Karnas E, Zuba-Surma E, Woznicka O, Pyza E, Kuleta P, Osyczka A, Rapala-Kozik M, Kozik A. Characteristics of Extracellular Vesicles Released by the Pathogenic Yeast-Like Fungi Candida glabrata, Candida parapsilosis and Candida tropicalis. Cells. 2020 Jul 18;9(7):1722. doi: 10.3390/cells9071722.
Katzmann DJ, Babst M, Emr SD. Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I. Cell. 2001 Jul 27;106(2):145-55. doi: 10.1016/s0092-8674(01)00434-2..
Katzmann DJ, Odorizzi G, Emr SD. Receptor downregulation and multivesicular-body sorting. Nat Rev Mol Cell Biol. 2002 Dec;3(12):893-905. doi: 10.1038/nrm973.
Kogure A, Yoshioka Y, Ochiya T. Extracellular Vesicles in Cancer Metastasis: Potential as Therapeutic Targets and Materials. Int J Mol Sci. 2020 Jun 23;21(12):4463. doi: 10.3390/ijms21124463.
Kostelansky MS, Sun J, Lee S, Kim J, Ghirlando R, Hierro A, Emr SD, Hurley JH. Structural and functional organization of the ESCRT-I trafficking complex. Cell. 2006 Apr 7;125(1):113-26. doi: 10.1016/j.cell.2006.01.049.
Kostelansky MS, Schluter C, Tam YY, Lee S, Ghirlando R, Beach B, Conibear E, Hurley JH. Molecular architecture and functional model of the complete yeast ESCRT-I heterotetramer. Cell. 2007 May 4;129(3):485-98. doi: 10.1016/j.cell.2007.03.016
Kowal J, Tkach M, Théry C. Biogenesis and secretion of exosomes. Curr Opin Cell Biol. 2014 Aug;29:116-25. doi: 10.1016/j.ceb.2014.05.004.
Liu J, Cvirkaite-Krupovic V, Commere PH, Yang Y, Zhou F, Forterre P, Shen Y, Krupovic M. Archaeal extracellular vesicles are produced in an ESCRT-dependent manner and promote gene transfer and nutrient cycling in extreme environments. ISME J. 2021 Oct;15(10):2892-2905. doi: 10.1038/s41396-021-00984-0.
Lu Q, Hope LW, Brasch M, Reinhard C, Cohen SN. TSG101 interaction with HRS mediates endosomal trafficking and receptor down-regulation. Proc Natl Acad Sci U S A. 2003 Jun 24;100(13):7626-31. doi: 10.1073/pnas.0932599100.
Lv Y, Tan J, Miao Y, Zhang Q. The role of microvesicles and its active molecules in regulating cellular biology. J Cell Mol Med. 2019 Dec;23(12):7894-7904. doi: 10.1111/jcmm.14667.
Machtinger R., Laurent L.C., Baccarelli A.A. Extracellular vesicles: Roles in gamete maturation, fertilization and embryo implantation. Hum. Reprod. Update. 2016;22:182–193. doi: 10.1093/humupd/dmv055.
Madeira F, Pearce M, Tivey ARN, et al. Search and sequence analysis tools services from EMBL-EBI in 2022. Nucleic Acids Research. 2022 Apr:gkac240. doi: 10.1093/nar/gkac240.
Marchesini N, Hannun YA. Acid and neutral sphingomyelinases: roles and mechanisms of regulation. Biochem Cell Biol. 2004 Feb;82(1):27-44. doi: 10.1139/o03-091.
Mathivanan S. Extracellular vesicles secreted by Saccharomyces cerevisiae are involved in cell wall remodelling. Commun Biol. 2019 Aug 9;2:305. doi: 10.1038/s42003-019-0538-8
Menck K, Sivaloganathan S, Bleckmann A, Binder C. Microvesicles in Cancer: Small Size, Large Potential. Int J Mol Sci. 2020 Jul 28;21(15):5373. doi: 10.3390/ijms21155373.
Midekessa G, Godakumara K, Ord J, Viil J, Lättekivi F, Dissanayake K, Kopanchuk S, Rinken A, Andronowska A, Bhattacharjee S, Rinken T, Fazeli A. Zeta Potential of Extracellular Vesicles: Toward Understanding the Attributes that Determine Colloidal Stability. ACS Omega. 2020 Jun 30;5(27):16701-16710. doi: 10.1021/acsomega.0c01582.
Mobarrez F, Sjövik C, Soop A, Hållström L, Frostell C, Pisetsky DS, Wallén H. CD40L expression in plasma of volunteers following LPS administration: A comparison between assay of CD40L on platelet microvesicles and soluble CD40L. Platelets. 2015;26(5):486-90. doi: 10.3109/09537104.2014.932339.
Nishida-Aoki N, Izumi Y, Takeda H, Takahashi M, Ochiya T, Bamba T. Lipidomic Analysis of Cells and Extracellular Vesicles from High- and Low-Metastatic Triple-Negative Breast Cancer. Metabolites. 2020 Feb 13;10(2):67. doi: 10.3390/metabo10020067.
Oliveira DL, Nakayasu ES, Joffe LS, Guimarães AJ, Sobreira TJ, Nosanchuk JD, Cordero RJ, Frases S, Casadevall A, Almeida IC, Nimrichter L, Rodrigues ML. Characterization of yeast extracellular vesicles: evidence for the participation of different pathways of cellular traffic in vesicle biogenesis. PLoS One. 2010 Jun 14;5(6):e11113. doi: 10.1371/journal.pone.0011113.
Oliver, J. 2021. ‘Saccharomyces cerevisiae communities share extracellular vesicles for protection from heat stress’. MSc (Biology) Thesis. Concordia University. Montreal, QC, Canada.
Platt, F.M., d’Azzo, A., Davidson, B.L. et al. Lysosomal storage diseases. Nat Rev Dis Primers 4, 27 (2018). https://doi.org/10.1038/s41572-018-0025-4
Pornillos O, Alam SL, Davis DR, Sundquist WI. Structure of the Tsg101 UEV domain in complex with the PTAP motif of the HIV-1 p6 protein. Nat Struct Biol. 2002 Nov;9(11):812-7. doi: 10.1038/nsb856.
Pornillos O, Alam SL, Rich RL, Myszka DG, Davis DR, Sundquist WI. Structure and functional interactions of the Tsg101 UEV domain. EMBO J. 2002 May 15;21(10):2397-406. doi: 10.1093/emboj/21.10.2397.
Poupardin R, Wolf M, Strunk D. Adherence to minimal experimental requirements for defining extracellular vesicles and their functions. Adv Drug Deliv Rev. 2021 Sep;176:113872. doi: 10.1016/j.addr.2021.113872.
Regimbeau M, Abrey J, Vautrot V, Causse S, Gobbo J, Garrido C. Heat shock proteins and exosomes in cancer theranostics. Semin Cancer Biol. 2022 Nov;86(Pt 1):46-57. doi: 10.1016/j.semcancer.2021.07.014..
Rizzo, J., Taheraly, Adam., Janbon, G. 2021. Structure, composition and biological properties of fungal extracellular vesicles. microLife, Volume 2, 2021, uqab009. doi.org/10.1093/femsml/uqab009
Rodrigues TA, Tuna KM, Alli AA, Tribulo P, Hansen PJ, Koh J, Paula-Lopes FF. Follicular fluid exosomes act on the bovine oocyte to improve oocyte competence to support development and survival to heat shock. Reprod Fertil Dev. 2019 Apr;31(5):888-897. doi: 10.1071/RD18450.
Safary A, Akbarzadeh Khiavi M, Mousavi R, Barar J, Rafi MA. Enzyme replacement therapies: what is the best option? Bioimpacts. 2018;8(3):153-157. doi: 10.15171/bi.2018.17.
Saksena S, Sun J, Chu T, Emr SD. ESCRTing proteins in the endocytic pathway. Trends Biochem Sci. 2007 Dec;32(12):561-73. doi: 10.1016/j.tibs.2007.09.010.
Santavanond JP, Rutter SF, Atkin-Smith GK, Poon IKH. Apoptotic Bodies: Mechanism of Formation, Isolation and Functional Relevance. Subcell Biochem. 2021;97:61-88. doi: 10.1007/978-3-030-67171-6_4.
Schmidt O, Teis D. The ESCRT machinery. Current Biology : CB. 2012 Feb;22(4):R116-20. doi: 10.1016/j.cub.2012.01.028.
Shao C, Yang F, Miao S, Liu W, Wang C, Shu Y, Shen H. Role of hypoxia-induced exosomes in tumor biology. Mol Cancer. 2018 Aug 11;17(1):120. doi: 10.1186/s12943-018-0869-y.
Skaar K, Korza HJ, Tarry M, Sekyrova P, Högbom M. Expression and Subcellular Distribution of GFP-Tagged Human Tetraspanin Proteins in Saccharomyces cerevisiae. PLoS One. 2015 Jul 28;10(7):e0134041. doi: 10.1371/journal.pone.0134041.
Skryabin GO, Komelkov AV, Savelyeva EE, Tchevkina EM. Lipid Rafts in Exosome Biogenesis. Biochemistry (Mosc). 2020 Feb;85(2):177-191. doi: 10.1134/S0006297920020054.
Slagsvold T, Pattni K, Malerød L, Stenmark H. Endosomal and non-endosomal functions of ESCRT proteins. Trends Cell Biol. 2006 Jun;16(6):317-26. doi: 10.1016/j.tcb.2006.04.004.
Sundquist WI, Schubert HL, Kelly BN, Hill GC, Holton JM, Hill CP. Ubiquitin recognition by the human TSG101 protein. Mol Cell. 2004 Mar 26;13(6):783-9. doi: 10.1016/s1097-2765(04)00129-7.
Taniguchi M, Okazaki T. Role of ceramide/sphingomyelin (SM) balance regulated through "SM cycle" in cancer. Cell Signal. 2021 Nov;87:110119. doi: 10.1016/j.cellsig.2021.110119.
The UniProt Consortium 2021. UniProt: the universal protein knowledge database in 2021. Nucleic Acids Res. 49:D480-D489(2021).
Thery, C., M. Boussac, P. Veron, P. Ricciardi-Castagnoli, G. Raposo, J. Garin, and S. Amigorena. 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.
Thery, C., M. Ostrowski, and E. Segura. 2009. Membrane vesicles as conveyors of immune responses. Nature reviews. 9:581-593. doi: 10.1038/nri2567
Thery, C., Witwer KW, Aikawa E., et al. 2018. 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 Nov 23;7(1):1535750. doi: 10.1080/20013078.2018.1535750.
Tucher C, Bode K, Schiller P, Claßen L, Birr C, Souto-Carneiro MM, Blank N, Lorenz HM, Schiller M. Extracellular Vesicle Subtypes Released From Activated or Apoptotic T-Lymphocytes Carry a Specific and Stimulus-Dependent Protein Cargo. Front Immunol. 2018 Mar 15;9:534. doi: 10.3389/fimmu.2018.00534..
Varadi, M., et al. 2021. Alpha Fold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Research.
Villarroya-Beltri C, Baixauli F, Gutiérrez-Vázquez C, Sánchez-Madrid F, Mittelbrunn M. Sorting it out: regulation of exosome loading. Semin Cancer Biol. 2014 Oct;28:3-13. doi: 10.1016/j.semcancer.2014.04.009.
Wijenayake S, Eisha S, Tawhidi Z, Pitino MA, Steele MA, Fleming AS, McGowan PO. Comparison of methods for pre-processing, exosome isolation, and RNA extraction in unpasteurized bovine and human milk. PLoS One. 2021 Sep 30;16(9):e0257633. doi: 10.1371/journal.pone.0257633.
Willms E, Cabañas C, Mäger I, Wood MJA, Vader P. Extracellular Vesicle Heterogeneity: Subpopulations, Isolation Techniques, and Diverse Functions in Cancer Progression. Front Immunol. 2018 Apr 30;9:738. doi: 10.3389/fimmu.2018.00738
Yáñez-Mó M, Siljander PR, Andreu Z, Zavec AB, Borràs FE, Buzas EI, Buzas K, Casal E, Cappello F, Carvalho J, Colás 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, Krämer-Albers EM, Laitinen S, Lässer C, Lener T, Ligeti E, Linē A, Lipps G, Llorente A, Lötvall J, Manček-Keber M, Marcilla A, Mittelbrunn M, Nazarenko I, Nolte-'t Hoen EN, Nyman TA, O'Driscoll L, Olivan M, Oliveira C, Pállinger É, Del Portillo HA, Reventós J, Rigau M, Rohde E, Sammar M, Sánchez-Madrid F, Santarém 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 May 14;4:27066. doi: 10.3402/jev.v4.27066.
Yang Y, Wang Y, Wei S, Zhou C, Yu J, Wang G, Wang W, Zhao L. Extracellular vesicles isolated by size-exclusion chromatography present suitability for RNomics analysis in plasma. J Transl Med. 2021 Mar 12;19(1):104. doi: 10.1186/s12967-021-02775-9.
Yu S, Cao H, Shen B, Feng J. Tumor-derived exosomes in cancer progression and treatment failure. Oncotarget. 2015 Nov 10;6(35):37151-68. doi: 10.18632/oncotarget.6022.
Zaborowski MP, Balaj L, Breakefield XO, Lai CP. Extracellular Vesicles: Composition, Biological Relevance, and Methods of Study. Bioscience. 2015 Aug 1;65(8):783-797. doi: 10.1093/biosci/biv084.
Zamith-Miranda D, Peres da Silva R, Couvillion SP, Bredeweg EL, Burnet MC, Coelho C, Camacho E, Nimrichter L, Puccia R, Almeida IC, Casadevall A, Rodrigues ML, Alves LR, Nosanchuk JD, Nakayasu ES. Omics Approaches for Understanding Biogenesis, Composition and Functions of Fungal Extracellular Vesicles. Front Genet. 2021 May 3;12:648524. doi: 10.3389/fgene.2021.648524
Zhang Y, Liu Y, Liu H, Tang WH. 2019. Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci. 2019 Feb 15;9:19. doi: 10.1186/s13578-019-0282-2.
Zhao K, Bleackley M, Chisanga D, Gangoda L, Fonseka P, Liem M, Kalra H, Al Saffar H, Keerthikumar S, Ang CS, Adda CG, Jiang L, Yap K, Poon IK, Lock P, Bulone V, Anderson M, Mathivanan S. Extracellular vesicles secreted by Saccharomyces cerevisiae are involved in cell wall remodelling. Commun Biol. 2019 Aug 9;2:305. doi: 10.1038/s42003-019-0538-8.
Zhu S, Li S, Yi M, Li N, Wu K. Roles of Microvesicles in Tumor Progression and Clinical Applications. Int J Nanomedicine. 2021 Oct 18;16:7071-7090. doi: 10.2147/IJN.S325448.
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