Open AccessQuantitative proteomics identifies the core proteome of exosomes with syntenin-1 as the highest abundant protein and a putative universal biomarker
Author(s) -
Fernanda G. Kugeratski,
Kelly Hodge,
Sérgio Lilla,
Kathleen M. McAndrews,
Zhou Xunian,
Rosa F. Hwang,
Sara Zanivan,
Raghu Kalluri
Publication year - 2021
Publication title -
nature cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 11.38
H-Index - 369
eISSN - 1476-4679
pISSN - 1465-7392
DOI - 10.1038/s41556-021-00693-y
Subject(s) - microvesicles , stable isotope labeling by amino acids in cell culture , proteome , proteomics , biology , quantitative proteomics , microbiology and biotechnology , biomarker , biogenesis , computational biology , biochemistry , microrna , gene
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.