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.
journal_name
Celljournal_title
Cellauthors
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 RJdoi
10.1016/j.cell.2019.02.029subject
Has Abstractpub_date
2019-04-04 00:00:00pages
428-445.e18issue
2eissn
0092-8674issn
1097-4172pii
S0092-8674(19)30212-0journal_volume
177pub_type
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