Differential proteomics argues against a general role for CD9, CD81 or CD63 in the sorting of proteins into extracellular vesicles.
CD63
CD81
CD9
IgSF8
PTGFRN
exosomes
extracellular vesicles
mass spectrometry
proteomic
tetraspanins
Journal
Journal of extracellular vesicles
ISSN: 2001-3078
Titre abrégé: J Extracell Vesicles
Pays: United States
ID NLM: 101610479
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
received:
06
03
2023
accepted:
15
07
2023
medline:
4
8
2023
pubmed:
1
8
2023
entrez:
1
8
2023
Statut:
ppublish
Résumé
The tetraspanins CD9, CD81 and CD63 are major components of extracellular vesicles (EVs). Yet, their impact on EV composition remains under-investigated. In the MCF7 breast cancer cell line CD63 was as expected predominantly intracellular. In contrast CD9 and CD81 strongly colocalized at the plasma membrane, albeit with different ratios at different sites, which may explain a higher enrichment of CD81 in EVs. Absence of these tetraspanins had little impact on the EV protein composition as analysed by quantitative mass spectrometry. We also analysed the effect of concomitant knock-out of CD9 and CD81 because these two tetraspanins play similar roles in several cellular processes and associate directly with two Ig domain proteins, CD9P-1/EWI-F/PTGFRN and EWI-2/IGSF8. These were the sole proteins significantly decreased in the EVs of double CD9- and CD81-deficient cells. In the case of EWI-2, this is primarily a consequence of a decreased cell expression level. In conclusion, this study shows that CD9, CD81 and CD63, commonly used as EV protein markers, play a marginal role in determining the protein composition of EVs released by MCF7 cells and highlights a regulation of the expression level and/or trafficking of CD9P-1 and EWI-2 by CD9 and CD81.
Identifiants
pubmed: 37525398
doi: 10.1002/jev2.12352
pmc: PMC10390663
doi:
Substances chimiques
Tetraspanin 28
0
Tetraspanin 29
0
CD63 protein, human
0
Tetraspanin 30
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12352Informations de copyright
© 2023 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.
Références
Andre, M., Chambrion, C., Charrin, S., Soave, S., Chaker, J., Boucheix, C., Rubinstein, E., & Le Naour, F. (2009). In situ chemical cross-linking on living cells reveals CD9P-1 cis-oligomer at cell surface. Journal of Proteomics, 73, 93-102.
Andre, M., Le Caer, J. P., Greco, C., Planchon, S., El Nemer, W., Boucheix, C., Rubinstein, E., Chamot-Rooke, J., & Le Naour, F. (2006). Proteomic analysis of the tetraspanin web using LC-ESI-MS/MS and MALDI-FTICR-MS. Proteomics, 6, 1437-1449.
Andreu, Z., & Yanez-Mo, M. (2014). Tetraspanins in extracellular vesicle formation and function. Frontiers in Immunology, 5, 442.
Andrijes, R., Hejmadi, R. K., Pugh, M., Rajesh, S., Novitskaya, V., Ibrahim, M., Overduin, M., Tselepis, C., Middleton, G. W., Győrffy, B., Beggs, A. D., & Berditchevski, F. (2021). Tetraspanin 6 is a regulator of carcinogenesis in colorectal cancer. Pnas, USA, 118(39), e2011411118.
Baietti, M. F., 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. Nature Cell Biology, 14, 677-685.
Bruening, J., Lasswitz, L., Banse, P., Kahl, S., Marinach, C., Vondran, F. W., Kaderali, L., Silvie, O., Pietschmann, T., Meissner, F., & Gerold, G. (2018). Hepatitis C virus enters liver cells using the CD81 receptor complex proteins calpain-5 and CBLB. Plos Pathogens, 14, e1007111.
Brzozowski, J. S., Bond, D. R., Jankowski, H., Goldie, B. J., Burchell, R., Naudin, C., Smith, N. D., Scarlett, C. J., Larsen, M. R., Dun, M. D., Skelding, K. A., & Weidenhofer, J. (2018). Extracellular vesicles with altered tetraspanin CD9 and CD151 levels confer increased prostate cell motility and invasion. Scientific Reports, 8, 8822.
Charrin, S., Jouannet, S., Boucheix, C., & Rubinstein, E. (2014). Tetraspanins at a glance. Journal of Cell Science, 127, 3641-3648.
Charrin, S., Latil, M., Soave, S., Polesskaya, A., Chretien, F., Boucheix, C., & Rubinstein, E. (2013). Normal muscle regeneration requires tight control of muscle cell fusion by tetraspanins CD9 and CD81. Nature Communications, 4, 1674.
Charrin, S., Le Naour, F., Labas, V., Billard, M., Le Caer, J. P., Emile, J. F., Petit, M. A., Boucheix, C., & Rubinstein, E. (2003). EWI-2 is a new component of the tetraspanin web in hepatocytes and lymphoid cells. Biochemical Journal, 373, 409-421.
Charrin, S., Le Naour, F., Oualid, M., Billard, M., Faure, G., Hanash, S. M., Boucheix, C., & Rubinstein, E. (2001). The major CD9 and CD81 molecular partner: Identification and characterization of the complexes. Journal of Biological Chemistry, 276, 14329-14337.
Charrin, S., Le Naour, F. L., Silvie, O., Milhiet, P. E., Boucheix, C., & Rubinstein, E. (2009). Lateral organization of membrane proteins: Tetraspanins spin their web. Biochemical Journal, 420, 133-154.
Charrin, S., Palmulli, R., Billard, M., Clay, D., Boucheix, C., Van Niel, G., & Rubinstein, E. (2020). Rapid isolation of rare isotype-switched hybridoma variants: Application to the generation of IgG2a and IgG2b MAb to CD63, a late endosome and exosome marker. Antibodies (Basel), 9, 29.
Charrin, S., Yalaoui, S., Bartosch, B., Cocquerel, L., Franetich, J. F., Boucheix, C., Mazier, D., Rubinstein, E., & Silvie, O. (2009). The Ig domain protein CD9P-1 down-regulates CD81 ability to support Plasmodium yoelii infection. Journal of Biological Chemistry, 284, 31572-31578.
Cohen, J., Wang, L., Marques, S., Ialy-Radio, C., Barbaux, S., Lefèvre, B., Gourier, C., & Ziyyat, A. (2022). Oocyte ERM and EWI proteins are involved in mouse fertilization. Frontiers in Cell and Developmental Biology, 10, 863729.
de Chaumont, F., Dallongeville, S., Chenouard, N., Herve, N., Pop, S., Provoost, T., Meas-Yedid, V., Pankajakshan, P., Lecomte, T., Montagner, Y. L., Lagache, T., Dufour, A., & Olivo-Marin, J. C. (2012). Icy: An open bioimage informatics platform for extended reproducible research. Nature Methods, 9, 690-696.
Dooley, K., McConnell, R. E., Xu, K., Lewis, N. D., Haupt, S., Youniss, M. R., Martin, S., Sia, C. L., McCoy, C., Moniz, R. J., Burenkova, O., Sanchez-Salazar, J., Jang, S. C., Choi, B., Harrison, R. A., Houde, D., Burzyn, D., Leng, C., Kirwin, K., … Williams, D. E. (2021). A versatile platform for generating engineered extracellular vesicles with defined therapeutic properties. Molecular Therapy, 29, 1729-1743.
Dornier, E., Coumailleau, F., Ottavi, J. F., Moretti, J., Boucheix, C., Mauduit, P., Schweisguth, F., & Rubinstein, E. (2012). TspanC8 tetraspanins regulate ADAM10/Kuzbanian trafficking and promote Notch activation in flies and mammals. Journal of Cell Biology, 199, 481-496.
Fordjour, F. K., Guo, C., Ai, Y., Daaboul, G. G., & Gould, S. J. (2022). A shared, stochastic pathway mediates exosome protein budding along plasma and endosome membranes. Journal of Biological Chemistry, 298, 102394.
Ghossoub, R., Chéry, M., Audebert, S., Leblanc, R., Egea-Jimenez, A. L., Lembo, F., Mammar, S., Dez, F. L., Camoin, L., Borg, J. P., Rubinstein, E., David, G., & Zimmermann, P. (2020). Tetraspanin-6 negatively regulates exosome production. PNAS, 117, 5913-5922.
Guix, F. X., Sannerud, R., Berditchevski, F., Arranz, A. M., Horré, K., Snellinx, A., Thathiah, A., Saido, T., Saito, T., Rajesh, S., Overduin, M., Kumar-Singh, S., Radaelli, E., Corthout, N., Colombelli, J., Tosi, S., Munck, S., Salas, I. H., Annaert, W., & De Strooper, B. (2017). Tetraspanin 6: A pivotal protein of the multiple vesicular body determining exosome release and lysosomal degradation of amyloid precursor protein fragments. Mol Neurodegener, 12, 25.
Haining, E. J., Yang, J., Bailey, R. L., Khan, K., Collier, R., Tsai, S., Watson, S. P., Frampton, J., Garcia, P., & Tomlinson, M. G. (2012). The TspanC8 subgroup of tetraspanins interacts with A disintegrin and metalloprotease 10 (ADAM10) and regulates its maturation and cell surface expression. Journal of Biological Chemistry, 287, 39753-39765.
Hamada, S., Pionneau, C., Parizot, C., Silvie, O., Chardonnet, S., & Marinach, C. (2021). In-depth proteomic analysis of Plasmodium berghei sporozoites using trapped ion mobility spectrometry with parallel accumulation-serial fragmentation. Proteomics, 21, e2000305.
He, Z. Y., Gupta, S., Myles, D., & Primakoff, P. (2009). Loss of surface EWI-2 on CD9 null oocytes. Molecular Reproduction and Development, 76, 629-636.
Hemler, M. E. (2005). Tetraspanin functions and associated microdomains. Nature Reviews Molecular Cell Biology, 6, 801-811.
Hurwitz, S. N., Cheerathodi, M. R., Nkosi, D., York, S. B., & Meckes, D. G. Jr (2018). Tetraspanin CD63 bridges autophagic and endosomal processes to regulate exosomal secretion and intracellular signaling of epstein-barr virus LMP1. Journal of Virology, 92, e01969.
Hurwitz, S. N., Rider, M. A., Bundy, J. L., Liu, X., Singh, R. K., & Meckes, D. G. Jr (2016). Proteomic profiling of NCI-60 extracellular vesicles uncovers common protein cargo and cancer type-specific biomarkers. Oncotarget, I, 86999-87015.
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., Fissell, W. H., Patton, J. G., Rome, L. H., Burnette, D. T., & Coffey, R. J. (2019). Reassessment of exosome composition. Cell, 177, e428-445e18.
Jouannet, S., Saint-Pol, J., Fernandez, L., Nguyen, V., Charrin, S., Boucheix, C., Brou, C., Milhiet, P. E., & Rubinstein, E. (2016). TspanC8 tetraspanins differentially regulate the cleavage of ADAM10 substrates, Notch activation and ADAM10 membrane compartmentalization. Cellular and Molecular Life Sciences, 73, 1895-1915.
Kalluri, R., & LeBleu, V. S. (2020). The biology, function, and biomedical applications of exosomes. Science, 367.
Kovalenko, O. V., Yang, X. H., & Hemler, M. E. (2007). A novel cysteine cross-linking method reveals a direct association between claudin-1 and tetraspanin CD9. Molecular & Cellular Proteomics, 6, 1855-1867.
Kowal, J., Arras, G., Colombo, M., Jouve, M., Morath, J. P., Primdal-Bengtson, B., Dingli, F., Loew, D., Tkach, M., & Thery, C. (2016). Proteomic comparison defines novel markers to characterize heterogeneous populations of extracellular vesicle subtypes. PNAS, 113, E968-E977.
Latysheva, N., Muratov, G., Rajesh, S., Padgett, M., Hotchin, N. A., Overduin, M., & Berditchevski, F. (2006). Syntenin-1 is a new component of tetraspanin-enriched microdomains: Mechanisms and consequences of the interaction of syntenin-1 with CD63. Molecular and Cellular Biology, 26, 7707-7718.
Le Naour, F., Andre, M., Greco, C., Billard, M., Sordat, B., Emile, J. F., Lanza, F., Boucheix, C., & Rubinstein, E. (2006). Profiling of the tetraspanin web of human colon cancer cells. Molecular & Cellular Proteomics, 5, 845-857.
Le Naour, F., Rubinstein, E., Jasmin, C., Prenant, M., & Boucheix, C. (2000). Severely reduced female fertility in CD9-deficient mice. Science, 287, 319-321.
Levy, S. (2014). Function of the tetraspanin molecule CD81 in B and T cells. Immunologic Research, 58(2-3), 179-185.
Lindenbergh, M. F. S., & Stoorvogel, W. (2018). Antigen presentation by extracellular vesicles from professional antigen-presenting cells. Annual Review of Immunology, 36, 435-459.
Lischnig, A., Bergqvist, M., Ochiya, T., & Lässer, C. (2022). Quantitative proteomics identifies proteins enriched in large and small extracellular vesicles. Molecular & Cellular Proteomics, 21, 100273.
Martin-Jaular, L., Nevo, N., Schessner, J. P., Tkach, M., Jouve, M., Dingli, F., Loew, D., Witwer, K. W., Ostrowski, M., Borner, G. H. H., & Théry, C. (2021). Unbiased proteomic profiling of host cell extracellular vesicle composition and dynamics upon HIV-1 infection. Embo Journal, 40, e105492.
Mathieu, M., Martin-Jaular, L., Lavieu, G., & Théry, C. (2019). Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication. Nature Cell Biology, 21, 9-17.
Mathieu, M., Névo, N., Jouve, M., Valenzuela, J. I., Maurin, M., Verweij, F. J., Palmulli, R., Lankar, D., Dingli, F., Loew, D., Rubinstein, E., Boncompain, G., Perez, F., & Théry, C. (2021). Specificities of exosome versus small ectosome secretion revealed by live intracellular tracking of CD63 and CD9. Nature Communications, 12, 4389.
Nabhan, J. F., Hu, R., Oh, R. S., Cohen, S. N., & Lu, Q. (2012). Formation and release of arrestin domain-containing protein 1-mediated microvesicles (ARMMs) at plasma membrane by recruitment of TSG101 protein. PNAS, 109, 4146-4151.
O'Connell, J. D., Paulo, J. A., O’Brien, J. J., & Gygi, S. P. (2018). Proteome-Wide Evaluation of Two Common Protein Quantification Methods. Journal of Proteome Research, 17(5), 1934-1942. https://doi.org/10.1021/acs.jproteome.8b00016
Oosterheert, W., Xenaki, K. T., Neviani, V., Pos, W., Doulkeridou, S., Manshande, J., Pearce, N. M., Kroon-Batenburg, L. M., Lutz, M., van Bergen En Henegouwen, P. M., & Gros, P. (2020). Implications for tetraspanin-enriched microdomain assembly based on structures of CD9 with EWI-F. Life Science Alliance, 3.
Pathan, M., Fonseka, P., Chitti, S. V., Kang, T., Sanwlani, R., Van Deun, J., Hendrix, A., & Mathivanan, S. (2019). Vesiclepedia 2019: A compendium of RNA, proteins, lipids and metabolites in extracellular vesicles. Nucleic Acids Research, 47, D516-D519.
Pathan, M., Keerthikumar, S., Chisanga, D., Alessandro, R., Ang, C. S., Askenase, P., Batagov, A. O., Benito-Martin, A., Camussi, G., Clayton, A., Collino, F., Di Vizio, D., Falcon-Perez, J. M., Fonseca, P., Fonseka, P., Fontana, S., Gho, Y. S., Hendrix, A., Hoen, E. N., … Mathivanan, S. (2017). A novel community driven software for functional enrichment analysis of extracellular vesicles data. Journal of Extracellular Vesicles, 6, 1321455.
Perez-Hernandez, D., Gutiérrez-Vázquez, C., Jorge, I., López-Martín, S., Ursa, A., Sánchez-Madrid, F., Vázquez, J., & Yáñez-Mó, M. (2013). The intracellular interactome of tetraspanin-enriched microdomains reveals their function as sorting machineries toward exosomes. Journal of Biological Chemistry, 288, 11649-11661.
Perez-Riverol, Y., Bai, J., Bandla, C., García-Seisdedos, D., Hewapathirana, S., Kamatchinathan, S., Kundu, D. J., Prakash, A., Frericks-Zipper, A., Eisenacher, M., Walzer, M., Wang, S., Brazma, A., & Vizcaíno, J. A. (2022). The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences. Nucleic Acids Research, 50, D543-D552.
Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., & Smyth, G. K. (2015). limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Research, 43, e47.
Rontogianni, S., Synadaki, E., Li, B., Liefaard, M. C., Lips, E. H., Wesseling, J., Wu, W., & Altelaar, M. (2019). Proteomic profiling of extracellular vesicles allows for human breast cancer subtyping. Communications Biology, 2, 325.
Rubinstein, E., Ziyyat, A., Prenant, M., Wrobel, E., Wolf, J. P., Levy, S., Le Naour, F., & Boucheix, C. (2006). Reduced fertility of female mice lacking CD81. Developmental Biology, 290, 351-358.
Sanjana, N. E., Shalem, O., & Zhang, F. (2014). Improved vectors and genome-wide libraries for CRISPR screening. Nature Methods, 11, 783-784.
Schröder, J., Lüllmann-Rauch, R., Himmerkus, N., Pleines, I., Nieswandt, B., Orinska, Z., Koch-Nolte, F., Schröder, B., Bleich, M., & Saftig, P. (2009). Deficiency of the tetraspanin CD63 associated with kidney pathology but normal lysosomal function. Molecular and Cellular Biology, 29, 1083-1094.
Schulze, U., Brast, S., Grabner, A., Albiker, C., Snieder, B., Holle, S., Schlatter, E., Schröter, R., Pavenstädt, H., Herrmann, E., Lambert, C., Spoden, G. A., Florin, L., Saftig, P., & Ciarimboli, G. (2017). Tetraspanin CD63 controls basolateral sorting of organic cation transporter 2 in renal proximal tubules. Faseb Journal, 31, 1421-1433.
Serru, V., Le Naour, F., Billard, M., Azorsa, D. O., Lanza, F., Boucheix, C., & Rubinstein, E. (1999). Selective tetraspan/integrin complexes (CD81/α4β1, CD151/α3β1, CD151/α6β1) under conditions disrupting tetraspan interactions. Biochemical Journal, 340, 103-111.
Sivanich, M. K., Gu, T., Tabang, D. N., & Li, L. (2022). Recent advances in isobaric labeling and applications in quantitative proteomics. PROTEOMICS, 22(19-20), 2100256. Portico. https://doi.org/10.1002/pmic.202100256
Stipp, C. S., Kolesnikova, T. V., & Hemler, M. E. (2001). EWI-2 is a major CD9 and CD81 partner and member of a novel ig protein subfamily. Journal of Biological Chemistry, 276, 40545-40554.
Stipp, C. S., Kolesnikova, T. V., & Hemler, M. E. (2003). EWI-2 regulates alpha3beta1 integrin-dependent cell functions on laminin-5. Journal of Cell Biology, 163, 1167-1177.
Stipp, C. S., Orlicky, D., & Hemler, M. E. (2001). FPRP, a major, highly stoichiometric, highly specific CD81- and CD9-associated protein. Journal of Biological Chemistry, 276, 4853-4862.
Stoeck, A., Keller, S., Riedle, S., Sanderson, M. P., Runz, S., Naour, F. L., Gutwein, P., Ludwig, A., Rubinstein, E., & Altevogt, P. (2006). A role for exosomes in the constitutive and stimulus-induced ectodomain cleavage of L1 and CD44. Biochemical Journal, 393, 609-618.
Suárez, H., Andreu, Z., Mazzeo, C., Toribio, V., Pérez-Rivera, A. E., López-Martín, S., García-Silva, S., Hurtado, B., Morato, E., Peláez, L., Arribas, E. A., Tolentino-Cortez, T., Barreda-Gómez, G., Marina, A. I., Peinado, H., & Yáñez-Mó, M. (2021). CD9 inhibition reveals a functional connection of extracellular vesicle secretion with mitophagy in melanoma cells. Journal of Extracellular Vesicles, 10, e12082.
Takeda, Y., Tachibana, I., Miyado, K., Kobayashi, M., Miyazaki, T., Funakoshi, T., Kimura, H., Yamane, H., Saito, Y., Goto, H., Yoneda, T., Yoshida, M., Kumagai, T., Osaki, T., Hayashi, S., Kawase, I., & Mekada, E. (2003). Tetraspanins CD9 and CD81 function to prevent the fusion of mononuclear phagocytes. Journal of Cell Biology, 161, 945-956.
Tkach, M., & Théry, C. (2016). Communication by extracellular vesicles: Where we are and where we need to go. Cell, 164, 1226-1232.
Tognoli, M. L., Dancourt, J., Bonsergent, E., Palmulli, R., de Jong, O. G., Van Niel, G., Rubinstein, E., Vader, P., & Lavieu, G. (2023). Lack of involvement of CD63 and CD9 tetraspanins in the extracellular vesicle content delivery process. Communications Biology, 6, 532.
Tyanova, S., Temu, T., & Cox, J. (2016). The MaxQuant computational platform for mass spectrometry-based shotgun proteomics. Nature Protocols, 11, 2301-2319.
van Niel, G., Charrin, S., Simoes, S., Romao, M., Rochin, L., Saftig, P., Marks, M. S., Rubinstein, E., & Raposo, G. (2011). The tetraspanin CD63 regulates ESCRT-independent and -dependent endosomal sorting during melanogenesis. Developmental Cell, 21, 708-721.
van Niel, G., D'Angelo, G., & Raposo, G. (2018). Shedding light on the cell biology of extracellular vesicles. Nature Reviews Molecular Cell Biology, 19, 213-228.
Weng, J., Krementsov, D. N., Khurana, S., Roy, N. H., & Thali, M. (2009). Formation of syncytia is repressed by tetraspanins in human immunodeficiency virus type 1-producing cells. Journal of Virology, 83, 7467-7474.
Whitaker, E. E., Matheson, N. J., Perlee, S., Munson, P. B., Symeonides, M., & Thali, M. (2019). EWI-2 inhibits cell-cell fusion at the HIV-1 virological presynapse. Viruses, 11.
Witwer, K. W., & Théry, C. (2019). Extracellular vesicles or exosomes? On primacy, precision, and popularity influencing a choice of nomenclature. Journal of Extracellular Vesicles, 8, 1648167.
Yáñez-Mó, M., Siljander, P. R., Andreu, Z., Zavec, A. B., Borràs, F. E., Buzas, E. I., Buzas, K., Casal, E., Cappello, F., Carvalho, J., Colás, E., Cordeiro-da Silva, A., Fais, S., Falcon-Perez, J. M., Ghobrial, I. M., Giebel, B., Gimona, M., Graner, M., Gursel, I., … De Wever, O. (2015). Biological properties of extracellular vesicles and their physiological functions. Journal of Extracellular Vesicles, 4, 27066.
Yauch, R. L., Berditchevski, F., Harler, M. B., Reichner, J., & Hemler, M. E. (1998). Highly stoichiometric, stable, and specific association of integrin alpha3beta1 with CD151 provides a major link to phosphatidylinositol 4-kinase, and may regulate cell migration. Molecular Biology of the Cell, 9, 2751-2765.
Zurek, N., Sparks, L., & Voeltz, G. (2011). Reticulon short hairpin transmembrane domains are used to shape ER tubules. Traffic (Copenhagen, Denmark), 12, 28-41.