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Protein Exosome Marker

Written/Edited by Dr. Stefan Pellenz, PhD

Abstract:
Exosomes are small (50-120nm) endosome derived extracellular microvesicles (EMV). They can contain a vast array of different proteins depending on their host cell which, and their components are further modulated by cellular state (e.g. stress or activation, or inhibition of specific signaling pathways).

What are Exosomes?

exosome biogenesis and protein markers

Exosome biogenesis (A) and protein exosome markers (B).

Exosomes were first observed in the early 1980s in the culture media of reticulocytes. They are produced in inward budding multivesicular bodies (MVBs). The resulting intra-luminal vesicles (ILV) are then released through exocytosis into the extracellular space. Based on early observations of this phenomena, the term “exosomes” was coined for such vesicles. Exosomes share similar topology to the plasma membrane and are released by virtually all cell types and have been confirmed in all bodily fluids (see Fig. A).

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Featured Exosome Marker Antibodies

CD63 Antibody (ABIN1440014)
  • Polyclonal CD63 antibody
  • For IF and Western Blotting
  • 5 PubMed References
CD63 Antibody (ABIN1440014)
CD9 antibody (ABIN969030)
  • Monoclonal Antibody [5G6] to CD9
  • For FACS, IHC, ELISA, WB
  • 2 PubMed References
CUT&RUN Pro Set ABIN6923138
CD24 Antibody (ABIN2749227)
  • Monoclonal Antibody [SN3]
  • Conjugated to APC
  • 6 PubMed References
Magnetic ConA Beads (Agarose) for CUT&RUN/CUT&Tag ABIN6952467
CD81 Antibody (ABIN2855163)
  • Polyclonal antibody to CD81
  • For ICC, FACS, IF, WB, IHC
  • 2 PubMed References
CUTANA pAG-MNase for ChIC/CUT&RUN ABIN6950951

How are Exosomes identified?

Exosomes can contain a vast array of different proteins depending on their host cell which, and their components are further modulated by cellular state (e.g. stress or activation, or inhibition of specific signaling pathways). Tetraspanins like CD9, CD63 and CD81 are the most common canonical exosome marker proteins, present on the vesicle surface. Surface localization of tetraspanin antigens makes them good candidate targets for immunolabeling and purification of exosomes from biological samples. Components of the endosomal sorting complex required for transport (ESCRT) like TSG101 and Alix, cytoskeletal proteins, integrins and annexins are also enriched on exosomes; these molecules play a pivotal role in exosome targeting and cell adhesion (see Fig. B).

How are Exosomes studied?

The exosome secretome is vast and diverse, containing many different markers (see http://www.exocarta.org/). However, the presence of canonical surface markers like those listed abovepermit purification and in-depth study of exosome secretion and content from different sample types.

antibodies-online offers a range of kits for exosome purification and quantification from human biological fluids (plasma, serum, urine, saliva) or cell-culture media, manufactured by BioVision. We also offer kits intended for extraction and purification of RNA and DNA from exosomes.

In addition to pre-generated assay kits, antibodies-online supplies you with a comprehensive selection of antibodies directed against known exosome proteins (see table).

Exosome marker related products

Protein Gene GeneID Uniprot Ref exocarta Top 100 proteins TS EF LP TA CS AG MT AP HS EN RG CA II VI ND
YWHAE7531P62258-22 X
YWHAZ7534P63104-15 X
HSPA53309P11021(1)35 X
ACTB60P60709-5 X
ADAM10102O14672(2)- XXX X
PDCD6IP10015Q8WUM4(3)2 X
ENO12023P06733(4)9 X
SNCA6622P37840(32)- X X
ANPEP290P15144-- X X
APP351P05067(5)- X
ANXA5308P08758(6)20 X X
ANXA2302P07355(7)6 X
JUN3725P05412-- XX
ACLY47P53396-72 X
ATP1A1476P05023-39 X
BSG 682P35613(8)- XX
CAV1857Q03135(9), (10)- X X
CD9928P21926(11)1X
ITGAL3683P20701(12)- X X
ITGAX3687P11215(12)- X X
ITGAM3684P20702(12)- X X
ITGB13688P05556(12)34 X X
CD37951P11049(11)-X
CD44960P16070(13)- X X
ITGA63655P23229(12)89 X X
CD63967P08962(10), (11)7X X
CD81975P60033(14)24X X
CD823732P27701(11)-X
TF2152P13726(15)- XX
MCAM4162P43121(15)- X X
CD1639332Q86VB7(15)- XXX
CLTC1213Q00610-23 X
CLDN19076O95832(8)- X
CFL11072P23528-25 X
--(16)- X
--(16)- X
EEF1A11915P68104(4)14 X
EEF21938P13639-17 X
EGFR1956P00533(15)- X
EPCAM4072P16422(17), (18)- X X
FASN2194P49327(3)21 X X
FLOT110211O75955(18), (19)41 X X
FLOT22319Q14254(19)- X
ALDOA226P04075-18 X
GAPDH2597P04406-4 X
--(20)- X
HSP90AA13320P07900(1)10 X X
HSP90AB13326P08238(1)19 X
HPSE10855Q9Y251(21)- X X
--(20)- X
--(20)- X
HLA-DRA3122P01903(22)- X XX
HLA-G3135P17693(23)- X XX
HSPA83312P11142(1)3 X
--(16)- X
Tax--(20)- X
HTT3064P42858(5)- X X
ICAM13383P05362(24)- X
LRRK2120892Q5S007(5)- X
LDHA3939P00338-13 X
LAMP13916P11279(25)- X X
LAMP23920P13473(23)88 X X
--(26)- X X
--(26)- X X
MUC14582P15941(15)- X X
CDH21000P19022(15)- X X
PGK15230P00558(4)16 X
ALPP250P05187(15)- X X
--(5)- X
KLK3354P07288(27)- X X
PKM5315P14618(28)12 X X
RAB1451552P61106-75 X
RAB5A5868P20339-80 X
RAB5B5869P61020-86 X
RAB5C5878P51148-64 X
RAB7A7879P51149-61 X
RAP1B5908P61224-33 X
SDC16382P18827(29)- X
SDC46385P31431(29)- X
SDCBP6386O00560(30)8 X
TAG-72--(15)- X
Tspan87103P19075(15)-X X
TSG1017251Q99816(31)11 X
VPS3555737Q96QK1(5)- X X

Get our exosome marker poster!

By clicking on the link below, you can download a copy of our Exosome poster as a PNG file.

Download a Copy

Why are Exosomes important?

Secretion of exosomes occurs constitutively though the rate of exosome secretion, and composition of exosomes may be augmented by a variety of intrinsic or extrinsic factors (e.g. cell stress, signaling cascades). Despite their ubiquitous nature, exosomes are considered unconventional secretory pathway components.

Because exomes are secreted from nearly every cell type, their composition mirrors their host diversity, and depends heavily upon the type of cell from which they originate.

Since the molecular composition of exosomes is reflective of physiological or pathophysiological changes in their cell or tissue of origin, studying exosome composition offers a significant potential to develop new biomarkers for disease diagnosis (see Table).

Note:

It has been suggested that SARS-CoV-2 may exploit the exosome transport based on studies showing that SARS-CoV is released from infected cell by exocyotosis. SARS-CoV-2 Nsp3, Nsp4, and Nsp6 also induce the formation of double-membrane vesicles (DMVs), suggesting a connection a role of exosomes in virus propagation. This might also enable the virus to evade immune detection and explain apparent reinfection of convalescent COVID-19 patients.33, 34, 35

Discover our COVID-19 tools and reagents

Exosomes are also a widely-implicated in cell-cell communication. Exosome components may be transferred directly to neighboring cells, or may be shuttled across a number of different cells before reaching their end destination via a method known as transcytosis. Exosomes can, therefore, be used to transmit signals across large distances where simple diffusion may be insufficient. Their role in cell-cell communication suggests that exosomes may have a deeper role in many physiological processes; this hypothesis is supported by the observation that exosome signaling plays a direct role in development & patterning, immune response, neuronal communication, and tissue repair.

Because of their small size (nano-scale) and simple structure, exosomes may sometimes cross the blood-brain barrier. Various futurists have suggested that exosome delivery systems may offer an innovative new technology to target the central nervous system and treating various cerebral/neuropathic diseases without necessitating invasive surgery. The use of exosomes to transfer genetic information, or to deliver therapeutic agents is a currently underexplored field that holds vast medicinal potential.

In some pathologies, exosomes also act as vectors; tumor cell-derived exosomes play an active role in tumor angiogenesis and metastasis. Exosomes shed from stimulated blood cells and the vascular endothelium are involved in neurological disorders such as multiple sclerosis, transient ischemic attacks, and antiphospholipid syndrome. Exosomes may also carry damaged cellular material targeted for destruction, in doing so they may facilitate the spreading of toxic forms of aggregated proteins such as α-synuclein, β-amyloid, and prion proteins and contribute to the progression of neurodegenerative diseases. Some research also suggests that exosome transport has been exploited by viral pathogens to travel between host cells and evade immune detection.


References

  1. Lancaster, Febbraio: "Exosome-dependent trafficking of HSP70: a novel secretory pathway for cellular stress proteins." in: The Journal of biological chemistry, Vol. 280, Issue 24, pp. 23349-55, (2005) (PubMed).
  2. Lin, Li, Huang, Liu, Chen, Chen, Xu, Huang, Wang: "Exosomes: novel biomarkers for clinical diagnosis." in: TheScientificWorldJournal, Vol. 2015, pp. 657086, (2016) (PubMed).
  3. Duijvesz, Burnum-Johnson, Gritsenko, Hoogland, Vredenbregt-van den Berg, Willemsen, Luider, Paša-Tolić, Jenster: "Proteomic profiling of exosomes leads to the identification of novel biomarkers for prostate cancer." in: PloS one, Vol. 8, Issue 12, pp. e82589, (2014) (PubMed).
  4. Yu, Harris, Levine: "The regulation of exosome secretion: a novel function of the p53 protein." in: Cancer research, Vol. 66, Issue 9, pp. 4795-801, (2006) (PubMed).
  5. Kalani, Tyagi: "Exosomes in neurological disease, neuroprotection, repair and therapeutics: problems and perspectives." in: Neural regeneration research, Vol. 10, Issue 10, pp. 1565-7, (2015) (PubMed).
  6. Li, Aliotta, Asara, Tucker, Quesenberry, Lally, Ramratnam: "Quantitative proteomic analysis of exosomes from HIV-1-infected lymphocytic cells." in: Proteomics, Vol. 12, Issue 13, pp. 2203-11, (2012) (PubMed).
  7. Valapala, Vishwanatha: "Lipid raft endocytosis and exosomal transport facilitate extracellular trafficking of annexin A2." in: The Journal of biological chemistry, Vol. 286, Issue 35, pp. 30911-30925, (2011) (PubMed).
  8. Li, Sherman-Baust, Tsai-Turton, Bristow, Roden, Morin: "Claudin-containing exosomes in the peripheral circulation of women with ovarian cancer." in: BMC cancer, Vol. 9, pp. 244, (2009) (PubMed).
  9. Svensson, Christianson, Wittrup, Bourseau-Guilmain, Lindqvist, Svensson, Mörgelin, Belting: "Exosome uptake depends on ERK1/2-heat shock protein 27 signaling and lipid Raft-mediated endocytosis negatively regulated by caveolin-1." in: The Journal of biological chemistry, Vol. 288, Issue 24, pp. 17713-24, (2013) (PubMed).
  10. Logozzi, De Milito, Lugini, Borghi, Calabrò, Spada, Perdicchio, Marino, Federici, Iessi, Brambilla, Venturi, Lozupone, Santinami, Huber, Maio, Rivoltini, Fais: "High levels of exosomes expressing CD63 and caveolin-1 in plasma of melanoma patients." in: PloS one, Vol. 4, Issue 4, pp. e5219, (2009) (PubMed).
  11. Andreu, Yáñez-Mó: "Tetraspanins in extracellular vesicle formation and function." in: Frontiers in immunology, Vol. 5, pp. 442, (2014) (PubMed).
  12. Hoshino, Costa-Silva, Shen, Rodrigues, Hashimoto, Tesic Mark, Molina, Kohsaka, Di Giannatale, Ceder, Singh, Williams, Soplop, Uryu, Pharmer, King, Bojmar, Davies, Ararso, Zhang, Zhang, Hernandez et al.: "Tumour exosome integrins determine organotropic metastasis. ..." in: Nature, Vol. 527, Issue 7578, pp. 329-35, (2015) (PubMed).
  13. Marhaba, Klingbeil, Nuebel, Nazarenko, Buechler, Zoeller: "CD44 and EpCAM: cancer-initiating cell markers." in: Current molecular medicine, Vol. 8, Issue 8, pp. 784-804, (2009) (PubMed).
  14. Welker, Reichert, Susser, Sarrazin, Martinez, Herrmann, Zeuzem, Piiper, Kronenberger: "Soluble serum CD81 is elevated in patients with chronic hepatitis C and correlates with alanine aminotransferase serum activity." in: PloS one, Vol. 7, Issue 2, pp. e30796, (2012) (PubMed).
  15. Jakobsen, Paulsen, Bæk, Varming, Sorensen, Jørgensen: "Exosomal proteins as potential diagnostic markers in advanced non-small cell lung carcinoma." in: Journal of extracellular vesicles, Vol. 4, pp. 26659, (2015) (PubMed).
  16. Meckes, Raab-Traub: "Microvesicles and viral infection." in: Journal of virology, Vol. 85, Issue 24, pp. 12844-54, (2012) (PubMed).
  17. Zhou, Mohamadi, Poudineh, Kermanshah, Ahmed, Safaei, Stojcic, Nam, Sargent, Kelley: "Interrogating Circulating Microsomes and Exosomes Using Metal Nanoparticles." in: Small (Weinheim an der Bergstrasse, Germany), Vol. 12, Issue 6, pp. 727-32, (2016) (PubMed).
  18. Jakobsen, Paulsen, Bæk, Varming, Sorensen, Jørgensen: "Exosomal proteins as potential diagnostic markers in advanced non-small cell lung carcinoma." in: Journal of extracellular vesicles, Vol. 4, pp. 26659, (2015) (PubMed).
  19. Otto, Nichols: "The roles of flotillin microdomains--endocytosis and beyond." in: Journal of cell science, Vol. 124, Issue Pt 23, pp. 3933-40, (2012) (PubMed).
  20. Chahar, Bao, Casola: "Exosomes and Their Role in the Life Cycle and Pathogenesis of RNA Viruses." in: Viruses, Vol. 7, Issue 6, pp. 3204-25, (2016) (PubMed).
  21. Thompson, Purushothaman, Ramani, Vlodavsky, Sanderson: "Heparanase regulates secretion, composition, and function of tumor cell-derived exosomes." in: The Journal of biological chemistry, Vol. 288, Issue 14, pp. 10093-10099, (2013) (PubMed).
  22. Arita, Baba, Shibata, Niiro, Shimoda, Isobe, Kusaba, Nakano, Harada: "B cell activation regulates exosomal HLA production." in: European journal of immunology, Vol. 38, Issue 5, pp. 1423-34, (2008) (PubMed).
  23. Carosella, Rouas-Freiss, Tronik-Le Roux, Moreau, LeMaoult: "HLA-G: An Immune Checkpoint Molecule." in: Advances in immunology, Vol. 127, pp. 33-144, (2015) (PubMed).
  24. Segura, Nicco, Lombard, Veron, Raposo, Batteux, Amigorena, Thery: "ICAM-1 on exosomes from mature dendritic cells is critical for efficient naive T-cell priming." in: Blood, Vol. 106, Issue 1, pp. 216-23, (2005) (PubMed).
  25. Chivet, Javalet, Laulagnier, Blot, Hemming, Sadoul: "Exosomes secreted by cortical neurons upon glutamatergic synapse activation specifically interact with neurons." in: Journal of extracellular vesicles, Vol. 3, pp. 24722, (2014) (PubMed).
  26. Nakayama: "Antigen Presentation by MHC-Dressed Cells." in: Frontiers in immunology, Vol. 5, pp. 672, (2015) (PubMed).
  27. Saini: "PSA and beyond: alternative prostate cancer biomarkers." in: Cellular oncology (Dordrecht), Vol. 39, Issue 2, pp. 97-106, (2016) (PubMed).
  28. Shinohara, Taniguchi, Kumazaki, Yamada, Ito, Otsuki, Uno, Hayakawa, Minami, Naoe, Akao: "Anti-cancer fatty-acid derivative induces autophagic cell death through modulation of PKM isoform expression profile mediated by bcr-abl in chronic myeloid leukemia." in: Cancer letters, Vol. 360, Issue 1, pp. 28-38, (2015) (PubMed).
  29. Baietti, Zhang, Mortier, Melchior, Degeest, Geeraerts, Ivarsson, Depoortere, Coomans, Vermeiren, Zimmermann, David: "Syndecan-syntenin-ALIX regulates the biogenesis of exosomes." in: Nature cell biology, Vol. 14, Issue 7, pp. 677-85, (2012) (PubMed).
  30. Ghossoub, Lembo, Rubio, Gaillard, Bouchet, Vitale, Slavík, Machala, Zimmermann: "Syntenin-ALIX exosome biogenesis and budding into multivesicular bodies are controlled by ARF6 and PLD2." in: Nature communications, Vol. 5, pp. 3477, (2014) (PubMed).
  31. Lee, El Andaloussi, Wood: "Exosomes and microvesicles: extracellular vesicles for genetic information transfer and gene therapy." in: Human molecular genetics, Vol. 21, Issue R1, pp. R125-34, (2013) (PubMed).
  32. Shi, Liu, Cook, Bullock, Zhao, Ginghina, Li, Aro, Dator, He, Hipp, Zabetian, Peskind, Hu, Quinn, Galasko, Banks, Zhang: "Plasma exosomal α-synuclein is likely CNS-derived and increased in Parkinson's disease." in: Acta neuropathologica, Vol. 128, Issue 5, pp. 639-650, (2015) (PubMed).

Additional References

  • (33) Qian, Z. et al. Innate immune response of human alveolar type II cells infected with severe acute respiratory syndrome-coronavirus. Am. J. Respir. Cell Mol. Biol. 48, 742–8 (2013).
  • (34) Elrashdy, F. et al. On the potential role of exosomes in the COVID-19 reinfection/reactivation opportunity. J. Biomol. Struct. Dyn. 1–12 (2020). doi:10.1080/07391102.2020.1790426
  • (35) Farkash, E. A. et al. Ultrastructural Evidence for Direct Renal Infection with SARS-CoV-2. J. Am. Soc. Nephrol. 31, 1683–1687 (2020).
Stefan Pellenz
Dr. Stefan Pellenz, PhD
Product Manager at antibodies-online.com

Goal-oriented, time line driven scientist, proficiently trained in different academic institutions in Germany, France and the USA. Experienced in the life sciences e-commerce environment with a focus on product development and customer relation management.

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