TY - JOUR
T1 - Quantitative proteomics identifies the core proteome of exosomes with syntenin-1 as the highest abundant protein and a putative universal biomarker
AU - Kugeratski, Fernanda G.
AU - Hodge, Kelly
AU - Lilla, Sergio
AU - McAndrews, Kathleen M.
AU - Zhou, Xunian
AU - Hwang, Rosa F.
AU - Zanivan, Sara
AU - Kalluri, Raghu
N1 - Funding Information:
We thank K. Dunner Jr. from the High-Resolution Electron Microscopy Facility at the MD Anderson Cancer Center (CCSG grant NIH P30CA016672) for assistance with transmission electron microscopy experiments; the staff at the Cytogenetics and Cell Authentication Core at MD Anderson Cancer Center for STR testing; the staff at the Advanced Technology MS Proteomic facility at the CRUK Beatson Institute (CRUK A17196); L.A. Snowden for technical support; K. Earl for assistance with SEC methodology; A. Haltom for generating tetraspanin knockdown lines; and M. Kirtley and L.J. Neilson for administrative support. The R.K. laboratory is supported by research funds from The University of Texas MD Anderson Cancer Center. The exosome-related research in the R.K. laboratory is funded by NCI R01 CA213233 and NCI R01 CA231465. F.G.K. funding as an Odyssey Fellow is supported by the Odyssey Program and Theodore N. Law for Scientific Achievement at The University of Texas MD Anderson Cancer Center. S.Z. funding is supported by Cancer Research UK (A29800).
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PY - 2021/6
Y1 - 2021/6
N2 - Exosomes are extracellular vesicles derived from the endosomal compartment that are potentially involved in intercellular communication. Here, we found that frequently used biomarkers of exosomes are heterogeneous, and do not exhibit universal utility across different cell types. To uncover ubiquitous and abundant proteins, we used an unbiased and quantitative proteomic approach based on super-stable isotope labeling with amino acids in cell culture (super-SILAC), coupled to high-resolution mass spectrometry. In total, 1,212 proteins were quantified in the proteome of exosomes, irrespective of the cellular source or isolation method. A cohort of 22 proteins was universally enriched. Fifteen proteins were consistently depleted in the proteome of exosomes compared to cells. Among the enriched proteins, we identified biogenesis-related proteins, GTPases and membrane proteins, such as CD47 and ITGB1. The cohort of depleted proteins in exosomes was predominantly composed of nuclear proteins. We identified syntenin-1 as a consistently abundant protein in exosomes from different cellular origins. Syntenin-1 is also present in exosomes across different species and biofluids, highlighting its potential use as a putative universal biomarker of exosomes. Our study provides a comprehensive quantitative atlas of core proteins ubiquitous to exosomes that can serve as a resource for the scientific community.
AB - Exosomes are extracellular vesicles derived from the endosomal compartment that are potentially involved in intercellular communication. Here, we found that frequently used biomarkers of exosomes are heterogeneous, and do not exhibit universal utility across different cell types. To uncover ubiquitous and abundant proteins, we used an unbiased and quantitative proteomic approach based on super-stable isotope labeling with amino acids in cell culture (super-SILAC), coupled to high-resolution mass spectrometry. In total, 1,212 proteins were quantified in the proteome of exosomes, irrespective of the cellular source or isolation method. A cohort of 22 proteins was universally enriched. Fifteen proteins were consistently depleted in the proteome of exosomes compared to cells. Among the enriched proteins, we identified biogenesis-related proteins, GTPases and membrane proteins, such as CD47 and ITGB1. The cohort of depleted proteins in exosomes was predominantly composed of nuclear proteins. We identified syntenin-1 as a consistently abundant protein in exosomes from different cellular origins. Syntenin-1 is also present in exosomes across different species and biofluids, highlighting its potential use as a putative universal biomarker of exosomes. Our study provides a comprehensive quantitative atlas of core proteins ubiquitous to exosomes that can serve as a resource for the scientific community.
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U2 - 10.1038/s41556-021-00693-y
DO - 10.1038/s41556-021-00693-y
M3 - Article
C2 - 34108659
AN - SCOPUS:85107474716
SN - 1465-7392
VL - 23
SP - 631
EP - 641
JO - Nature cell biology
JF - Nature cell biology
IS - 6
ER -