Protein glycosylation in extracellular vesicles: Structural characterization and biological functions

Mol Immunol. 2021 Jul:135:226-246. doi: 10.1016/j.molimm.2021.04.017. Epub 2021 Apr 29.

Abstract

Extracellular vesicles (EVs) are lipid bilayer-enclosed particles involved in intercellular communication, delivery of biomolecules from donor to recipient cells, cellular disposal and homeostasis, potential biomarkers and drug carriers. The content of EVs includes DNA, lipids, metabolites, proteins, and microRNA, which have been studied in various diseases, such as cancer, diabetes, pregnancy, neurodegenerative, and cardiovascular disorders. EVs are enriched in glycoconjugates and exhibit specific glycosignatures. Protein glycosylation is a co- and post-translational modification (PTM) that plays an important role in the expression and function of exosomal proteins. N- and O-linked protein glycosylation has been mapped in exosomal proteins. The purpose of this review is to highlight the importance of glycosylation in EVs proteins. Initially, we describe the main PTMs in EVs with a focus on glycosylation. Then, we explore glycan-binding proteins describing the main findings of studies that investigated the glycosylation of EVs in cancer, pregnancy, infectious diseases, diabetes, mental disorders, and animal fluids. We have highlighted studies that have developed innovative methods for studying the content of EVs. In addition, we present works related to lipid glycosylation. We explored the content of studies deposited in public databases, such as Exocarta and Vesiclepedia. Finally, we discuss analytical methods for structural characterization of glycoconjugates and present an overview of the critical points of the study of glycosylation EVs, as well as perspectives in this field.

Keywords: Extracellular vesicles; Glycoconjugates; Glycomics; Glycoproteomics; Glycosylation; Lectins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carrier Proteins / metabolism*
  • Cell Communication / physiology*
  • Exosomes / metabolism*
  • Extracellular Vesicles / metabolism
  • Glycosylation
  • Humans
  • Neoplasms / pathology
  • Polysaccharides / metabolism*
  • Protein Binding / physiology
  • Protein Processing, Post-Translational / physiology*

Substances

  • Carrier Proteins
  • Polysaccharides