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, researchers from Vanderbilt University Medical Center 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 were not detected in exosomes. The researchers identify annexin A1 as a specific marker for microvesicles that are shed directly from the plasma membrane. They further show that small extracellular vesicles are not vehicles of active DNA release. Instead, they 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.
Reassessment of exosome composition
Jeppesen DK, Fenix AM, Franklin JL, Higginbotham JN, Zhang Q, Zimmerman LJ, Liebler DC, Ping J, Liu Q, Evans R, Fissell WH, Patton JG, Rome LH, Burnette DT, Coffey RJ. (2022) Reassessment of Exosome Composition. Cell 4;177(2):428-445.e18. [article]