Reassessment of Exosome Composition

Cell. 2019 Apr 4;177(2):428-445.e18. doi: 10.1016/j.cell.2019.02.029.


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.

Keywords: Argonaute; amphisomes; annexin; autophagy; exomeres; exosomes; extracellular DNA; extracellular RNA; extracellular vesicles; microvesicles.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Annexin A1 / metabolism
  • Argonaute Proteins / metabolism
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cell-Derived Microparticles / metabolism
  • DNA / metabolism
  • Exosomes / chemistry
  • Exosomes / metabolism*
  • Exosomes / physiology*
  • Extracellular Vesicles
  • Female
  • Humans
  • Lysosomes / metabolism
  • Male
  • Proteins / metabolism
  • RNA / metabolism


  • Annexin A1
  • Argonaute Proteins
  • Proteins
  • RNA
  • DNA