Review
Oxidative and other posttranslational modifications in extracellular vesicle biology

https://doi.org/10.1016/j.semcdb.2015.02.012Get rights and content

Highlights

  • Extracellular vesicles are increasingly recognised players of intercellular communication.

  • Most frequently studied posttranslational modifications include glycosylation, phosphorylation, oxidation and citrullination.

  • Posttranslational modifications have major impact on vesicle biogenesis, cargo sorting and vesicular uptake.

  • Enzymes capable of carrying out posttranslational modifications are transported by extracellular vesicles.

  • Characteristic posttranslational modifications of extracellular vesicle proteins may associate with specific pathophysiological processes.

Abstract

Extracellular vesicles including exosomes, microvesicles and apoptotic vesicles, are phospholipid bilayer surrounded structures secreted by cells universally, in an evolutionarily conserved fashion. Posttranslational modifications such as oxidation, citrullination, phosphorylation and glycosylation play diverse roles in extracellular vesicle biology. Posttranslational modifications orchestrate the biogenesis of extracellular vesicles. The signals extracellular vesicles transmit between cells also often function via modulating posttranslational modifications of target molecules, given that extracellular vesicles are carriers of several active enzymes catalysing posttranslational modifications. Posttranslational modifications of extracellular vesicles can also contribute to disease pathology by e.g. amplifying inflammation, generating neoepitopes or carrying neoepitopes themselves.

Section snippets

Extracellular vesicles

Extracellular vesicles (EVs) are phopholipid bilayer bound structures secreted actively by most, if not all, types of cells. For a long time they remained unnoticed, partially because the resolution of light microscopy did not permit their identification. On the other hand, the widely used collective term “cell debris” obscured and misleadingly tagged any submicron structures as waste products. In fact, certain EVs have been known for almost half a century such as matrix vesicles in cartilage

Posttranslational modifications of extracellular vesicles

A wide range of PTMs can occur on many amino acids in vivo and greatly contribute to protein diversity and regulation. Amongst the most extensively studied of these PTMs are phosphorylation, ubiquitination and oxidation, each with numerous effects on their downstream targets. The effects of PTMs on cells are diverse from homeostatic signalling cascades to pathogenic loss/gain of function of proteins that result in cell senescence or the induction of apoptosis.

The role of PTMs in driving

Summary and outlook

PTMs regulate and fine-tune mechanisms of cellular communication and immune function. PTMs are therefore central to the physiological functions of the immune system. On the other hand, PTMs are often involved in the pathology of a number of conditions such as cancer, autoimmunity, atherosclerosis and neurodegenerative diseases. Presently, there is an emerging awareness of the PTM-directed regulation of EV function or pathology (Fig. 1, Fig. 2). Redox processes, phosphorylation, ubiquitination

Acknowledgments

This work was funded OTKA PD104369, by OTKA NK 84043, and Marie Curie Networks for Initial Training-ITN-FP7-PEOPLE-2011-ITN, PITN-GA-2011-289033, and ME-HAD (COST Action BM1202).

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