Reassessment of Exosome Composition

By D. K. Jeppesen, Aidan M. Fenix, J. Franklin, J. Higginbotham, Qin Zhang, L. Zimmerman, D. Liebler, J. Ping, Qi Liu, Rachel C. Evans and 5 more. Cell, 2019

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SUMMARY The heterogeneity of small extracellular vesicles and presence of non-vesicular extracellular matter have led to debate about contents and functional properties of exosomes. Here, we employ high-resolution density gradient fractionation and direct immunoaffinity capture to precisely characterize the RNA, DNA, and protein constituents of exosomes and other non-vesicle material. Extracellular RNA, RNA-binding proteins and other cellular proteins are differentially expressed in exosomes and non-vesicle compartments. Argonaute 1–4, glycolytic enzymes and cytoskeletal proteins are absent from exosomes. We identify Annexin A1 as a specific marker for microvesicles that are shed directly from the plasma membrane. We further show that small extracellular vesicles are not vehicles of active DNA release. Instead, we propose a new model for active secretion of extracellular DNA through an autophagy- and multivesicular endosome-dependent, but exosome-independent mechanism. This study demonstrates the need for a reassessment of exosome composition and offers a framework for a clearer understanding of extracellular vesicle heterogeneity.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/d1b801b54205997993f3299ba17ac80549aca741

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