Abstract
Exosomes feature a high protein-to-lipid ratio as reported by Subra et al. [1]. However, the lipid phase and lipid mediators participate in biological activity of these vesicles. The lipid composition, membrane organization, metabolic pathways operating within exosomes, and the effects of exosomal bioactive lipids in target cells are described.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Subra C, Laulagnier K, Perret B, Record M (2007) Exosome lipidomics unravels lipid sorting at the level of multivesicular bodies. Biochimie 89:205–212
Record M, Subra C, Silvente-Poirot S, Poirot M (2011) Exosomes as intercellular signalosomes and pharmacological effectors. Biochem Pharmacol 81:1171–1182
Thery C, Ostrowski M, Segura E (2009) Membrane vesicles as conveyors of immune responses. Nat Rev Immunol 9:581–593
Zhou L, Choi HY, Li WP, Xu F, Herz J (2009) LRP1 controls cPLA2 phosphorylation, ABCA1 expression and cellular cholesterol export. PLoS ONE 4:e6853
Laulagnier K, Motta C, Hamdi S, Roy S, Fauvelle F, Pageaux JF et al (2004) Mast cell- and dendritic cell-derived exosomes display a specific lipid composition and an unusual membrane organization. Biochem J 380:161–171
Miyanishi M, Tada K, Koike M, Uchiyama Y, Kitamura T, Nagata S (2007) Identification of Tim4 as a phosphatidylserine receptor. Nature 450:435–439
Zakharova L, Svetlova M, Fomina AF (2007) T cell exosomes induce cholesterol accumulation in human monocytes via phosphatidylserine receptor. J Cell Physiol 212:174–181
Blanc L, Barres C, Bette-Bobillo P, Vidal M (2007) Reticulocyte-secreted exosomes bind natural IgM antibodies: involvement of a ROS-activatable endosomal phospholipase iPLA2. Blood 110:3407–3416
Luketic L, Delanghe J, Sobol PT, Yang P, Frotten E, Mossman KL et al (2007) Antigen presentation by exosomes released from peptide-pulsed dendritic cells is not suppressed by the presence of active CTL. J Immunol 179:5024–5032
Carayon K, Chaoui K, Ronzier E, Lazar I, Bertrand-Michel J, Roques V et al (2011) The proteo-lipidic composition of exosomes changes during reticulocyte maturation. J Biol Chem 286:34426–34439
Wubbolts R, Leckie RS, Veenhuizen PT, Schwarzmann G, Mobius W, Hoernschemeyer J et al (2003) Proteomic and biochemical analyses of human B cell-derived exosomes. Potential implications for their function and multivesicular body formation. J Biol Chem 278:10963–10972
Trajkovic K, Hsu C, Chiantia S, Rajendran L, Wenzel D, Wieland F et al (2008) Ceramide triggers budding of exosome vesicles into multivesicular endosomes. Science 319:1244–1247
Parolini I, Federici C, Raggi C, Lugini L, Palleschi S, De Milito A et al (2009) Microenvironmental pH is a key factor for exosome traffic in tumor cells. J Biol Chem 284:34211–34222
Fomina AF, Deerinck TJ, Ellisman MH, Cahalan MD (2003) Regulation of membrane trafficking and subcellular organization of endocytic compartments revealed with FM1-43 in resting and activated human T cells. Exp Cell Res 291:150–166
Pais-Correia AM, Sachse M, Guadagnini S, Robbiati V, Lasserre R, Gessain A et al (2010) Biofilm-like extracellular viral assemblies mediate HTLV-1 cell-to-cell transmission at virological synapses. Nat Med 16:83–89
de Gassart A, Geminard C, Fevrier B, Raposo G, Vidal M (2003) Lipid raft-associated protein sorting in exosomes. Blood 102:4336–4344
Lhermusier T, Chap H, Payrastre B (2011) Platelet membrane phospholipid asymmetry: from the characterization of a scramblase activity to the identification of an essential protein mutated in Scott syndrome. J Thromb Haemost 9:1883–1891
Zachowski A (1993) Phospholipids in animal eukaryotic membranes: transverse asymmetry and movement. Biochem J 294 (Pt 1):1–14
Subra C, Grand D, Laulagnier K, Stella A, Lambeau G, Paillasse M et al (2010) Exosomes account for vesicle-mediated transcellular transport of activatable phospholipases and prostaglandins. J Lipid Res 51:2105–2120
Wang D, Dubois RN (2010) Eicosanoids and cancer. Nat Rev Cancer 10:181–193
Esser J, Gehrmann U, D’Alexandri FL, Hidalgo-Estevez AM, Wheelock CE, Scheynius A et al (2010) Exosomes from human macrophages and dendritic cells contain enzymes for leukotriene biosynthesis and promote granulocyte migration. J Allergy Clin Immunol 126:1032–1040 (40 e1–4)
Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659
Folco G, Murphy RC (2006) Eicosanoid transcellular biosynthesis: from cell-cell interactions to in vivo tissue responses. Pharmacol Rev 58:375–388
Laulagnier K, Vincent-Schneider H, Hamdi S, Subra C, Lankar D, Record M (2005) Characterization of exosome subpopulations from RBL-2H3 cells using fluorescent lipids. Blood Cells Mol Dis 35:116–121
Foster DA (2007) Regulation of mTOR by phosphatidic acid? Cancer Res 67:1–4
Samadi N, Bekele R, Capatos D, Venkatraman G, Sariahmetoglu M, Brindley DN (2011) Regulation of lysophosphatidate signaling by autotaxin and lipid phosphate phosphatases with respect to tumor progression, angiogenesis, metastasis and chemo-resistance. Biochimie 93:61–70
Laulagnier K, Grand D, Dujardin A, Hamdi S, Vincent-Schneider H, Lankar D et al (2004) PLD2 is enriched on exosomes and its activity is correlated to the release of exosomes. FEBS Lett 572:11–14
Reue K, Brindley DN (2008) Thematic review series: glycerolipids. Multiple roles for lipins/phosphatidate phosphatase enzymes in lipid metabolism. J Lipid Res 49:2493–2503
Alonso R, Mazzeo C, Rodriguez MC, Marsh M, Fraile-Ramos A, Calvo V et al (2011) 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 18:1161–1173
Cheng H, Sukal S, Callender R, Leyh TS (2001) gamma-phosphate protonation and pH-dependent unfolding of the Ras.GTP.Mg2 + complex: a vibrational spectroscopy study. J Biol Chem 276:9931–9935
Heo J, Gao G, Campbell SL (2004) pH-Dependent perturbation of Ras-guanine nucleotide interactions and Ras guanine nucleotide exchange. Biochemistry 43:10102–10111
van Blitterswijk WJ, Hilkmann H (1993) Rapid attenuation of receptor-induced diacylglycerol and phosphatidic acid by phospholipase D-mediated transphosphatidylation: formation of bisphosphatidic acid. Embo J 12:2655–2662
Kobayashi T, Beuchat MH, Chevallier J, Makino A, Mayran N, Escola JM et al (2002) Separation and characterization of late endosomal membrane domains. J Biol Chem 277:32157–32164
van Rossum DB, Oberdick D, Rbaibi Y, Bhardwaj G, Barrow RK, Nikolaidis N et al (2008) TRP_2, a lipid/trafficking domain that mediates diacylglycerol-induced vesicle fusion. J Biol Chem 283:34384–34392
Kobayashi T, Beuchat MH, Lindsay M, Frias S, Palmiter RD, Sakuraba H et al (1999) Late endosomal membranes rich in lysobisphosphatidic acid regulate cholesterol transport. Nat Cell Biol 1:113–118
Delton-Vandenbroucke I, Bouvier J, Makino A, Besson N, Pageaux JF, Lagarde M et al (2007) Anti-bis(monoacylglycero)phosphate antibody accumulates acetylated LDL-derived cholesterol in cultured macrophages. J Lipid Res 48:543–552
Bouvier J, Zemski Berry KA, Hullin-Matsuda F, Makino A, Michaud S, Geloen A et al (2009) Selective decrease of bis(monoacylglycero)phosphate content in macrophages by high supplementation with docosahexaenoic acid. J Lipid Res 50:243–255
Chevallier J, Chamoun Z, Jiang G, Prestwich G, Sakai N, Matile S et al (2008) Lysobisphosphatidic acid controls endosomal cholesterol levels. J Biol Chem 283:27871–27880
Paillasse MR, de Medina P, Amouroux G, Mhamdi L, Poirot M, Silvente-Poirot S (2009) Signaling through cholesterol esterification: a new pathway for the cholecystokinin 2 receptor involved in cell growth and invasion. J Lipid Res 50:2203–2211
Mathivanan S, Fahner CJ, Reid GE, Simpson RJ (2011) ExoCarta 2012: database of exosomal proteins, RNA and lipids. Nucleic Acids Res:1–4
Taguchi R, Ishikawa M (2010) Precise and global identification of phospholipid molecular species by an orbitrap mass spectrometer and automated search engine lipid search. J Chromatogr A 1217:4229–4239
Feng D, Zhao WL, Ye YY, Bai XC, Liu RQ, Chang LF et al (2010) Cellular internalization of exosomes occurs through phagocytosis. Traffic 11:675–687
Meyer zu Heringdorf D, Jakobs KH (2007) Lysophospholipid receptors: signalling, pharmacology and regulation by lysophospholipid metabolism. Biochim Biophys Acta 1768:923–940
Freeman GJ, Casasnovas JM, Umetsu DT, DeKruyff RH (2010) TIM genes: a family of cell surface phosphatidylserine receptors that regulate innate and adaptive immunity. Immunol Rev 235:172–89
Radu CG, Yang LV, Riedinger M, Au M, Witte ON (2004) T cell chemotaxis to lysophosphatidylcholine through the G2A receptor. Proc Natl Acad Sci U S A 101:245–250
Perrin-Cocon L, Agaugue S, Coutant F, Masurel A, Bezzine S, Lambeau G et al (2004) Secretory phospholipase A2 induces dendritic cell maturation. Eur J Immunol 34:2293–2302
Wang D, Dubois RN (2010) The role of COX-2 in intestinal inflammation and colorectal cancer. Oncogene 29:781–788
Mansure JJ, Nassim R, Kassouf W (2009) Peroxisome proliferator-activated receptor gamma in bladder cancer: a promising therapeutic target. Cancer Biol Ther 8:6–15
Skokos D, Botros HG, Demeure C, Morin J, Peronet R, Birkenmeier G et al (2003) Mast cell-derived exosomes induce phenotypic and functional maturation of dendritic cells and elicit specific immune responses in vivo. J Immunol 170:3037–3045
Lalier L, Cartron PF, Pedelaborde F, Olivier C, Loussouarn D, Martin SA et al (2007) Increase in PGE2 biosynthesis induces a Bax dependent apoptosis correlated to patients’ survival in glioblastoma multiforme. Oncogene 26:4999–5009
Chan BS, Satriano JA, Pucci M, Schuster VL (1998) Mechanism of prostaglandin E2 transport across the plasma membrane of HeLa cells and Xenopus oocytes expressing the prostaglandin transporter “PGT.” J Biol Chem 273:6689–6697
Xiang X, Poliakov A, Liu C, Liu Y, Deng ZB, Wang J et al (2009) Induction of myeloid-derived suppressor cells by tumor exosomes. Int J Cancer 124:2621–2633
Huang Q, Li F, Liu X, Li W, Shi W, Liu FF et al (2011) Caspase 3-mediated stimulation of tumor cell repopulation during cancer radiotherapy. Nat Med 17:860–866
Sertznig P, Seifert M, Tilgen W, Reichrath J (2007) Present concepts and future outlook: function of peroxisome proliferator-activated receptors (PPARs) for pathogenesis, progression, and therapy of cancer. J Cell Physiol 212:1–12
Amigorena S, Savina A (2010) Intracellular mechanisms of antigen cross presentation in dendritic cells. Curr Opin Immunol 22:109–117
Chakravarthy MV, Lodhi IJ, Yin L, Malapaka RR, Xu HE, Turk J et al (2009) Identification of a physiologically relevant endogenous ligand for PPARalpha in liver. Cell 138:476–488
Bougnoux P, Hajjaji N, Maheo K, Couet C, Chevalier S (2010) Fatty acids and breast cancer: sensitization to treatments and prevention of metastatic re-growth. Prog Lipid Res 49:76–86
de Medina P, Payre B, Boubekeur N, Bertrand-Michel J, Terce F, Silvente-Poirot S et al (2009) Ligands of the antiestrogen-binding site induce active cell death and autophagy in human breast cancer cells through the modulation of cholesterol metabolism. Cell Death Differ 16:1372–1384
de Medina P, Paillasse MR, Segala G, Poirot M, Silvente-Poirot S (2010) Identification and pharmacological characterization of cholesterol-5,6-epoxide hydrolase as a target for tamoxifen and AEBS ligands. Proc Natl Acad Sci U S A 107:13520–13525
de Medina P, Paillasse MR, Segala G, Khallouki F, Brillouet S, Dalenc F et al (2011) Importance of cholesterol and oxysterols metabolism in the pharmacology of tamoxifen and other AEBS ligands. Chem Phys Lipids 164:432–437
Zhuang X, Xiang X, Grizzle W, Sun D, Zhang S, Axtell RC et al (2011) Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol Ther 19:1769–1779
de Medina P, Paillasse MR, Payre B, Silvente-Poirot S, Poirot M (2009) Synthesis of new alkylaminooxysterols with potent cell differentiating activities: identification of leads for the treatment of cancer and neurodegenerative diseases. J Med Chem 52:7765–7777
Silvente-Poirot S, Record M, de Medina P, Subra C, Payré B, Paillasse MR et al (2011) Dendrogenin A modifies agressive melanoma cells to secrete exosomes with antitumor activity. International Workshop on Exosomes, January 19–22, Paris, France
Wang P, Zhang Y, Li H, Chieu HK, Munn AL, Yang H (2005) AAA ATPases regulate membrane association of yeast oxysterol binding proteins and sterol metabolism. EMBO J 24:2989–2999
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this chapter
Cite this chapter
Record, M. (2013). Exosomal Lipids in Cell–Cell Communication. In: Zhang, HG. (eds) Emerging Concepts of Tumor Exosome–Mediated Cell-Cell Communication. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3697-3_3
Download citation
DOI: https://doi.org/10.1007/978-1-4614-3697-3_3
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-3696-6
Online ISBN: 978-1-4614-3697-3
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)