Reassessment of Exosome Composition

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2019 Apr 6

PMID 30951670

Citations 1315

Authors

Dennis K Jeppesen

Aidan M Fenix

Jeffrey L Franklin

James N Higginbotham

Qin Zhang

Lisa J Zimmerman

Daniel C Liebler

Jie Ping

Qi Liu

Rachel Evans

William H Fissell

James G Patton

Leonard H Rome

Dylan T Burnette

Robert J Coffey

Affiliations

Soon will be listed here.

Abstract

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 were not detected in 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.

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