The Role of Post-Translational Modifications in Targeting Protein Cargo to Extracellular Vesicles

Subcell Biochem. 2021;97:45-60. doi: 10.1007/978-3-030-67171-6_3.


Extracellular vesicles (EVs) are naturally occurring nanoparticles that contain proteins and nucleic acids. It is speculated that cells release EVs loaded with a selective cargo of proteins through highly regulated processes. Several proteomic and biochemical studies have highlighted phosphorylated, glycosylated, ubiquitinated, SUMOylated, oxidated and palmitoylated proteins within the EVs. Emerging evidences suggest that post-translational modifications (PTMs) can regulate the sorting of specific proteins into EVs and such proteins with specific PTMs have also been identified in clinical samples. Hence, it has been proposed that EV proteins with PTMs could be used as potential biomarkers of disease conditions. Among the other cellular mechanisms, the endosomal sorting complex required for transport (ESCRT) is also implicated in cargo sorting into EVs. In this chapter, various PTMs that are shown to regulate protein cargo sorting into EVs will be discussed.

Keywords: Cargo sorting; Exosomes; Extracellular vesicles; Glycosylation; ISGylation; Myristoylation; Oxidation; Palmitoylation; Phosphorylation; Post-translational modifications; SUMOylation; Ubiquitination.

MeSH terms

  • Extracellular Vesicles* / metabolism
  • Protein Processing, Post-Translational
  • Protein Transport
  • Proteins / metabolism
  • Proteomics*


  • Proteins