ReviewOxidative and other posttranslational modifications in extracellular vesicle biology
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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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2020, Free Radical Biology and MedicineCitation Excerpt :Such an oxidation within the producer cell has been described to promote EV release by various mechanisms [43,55]. When studied, such a release is recurrently proposed as a protective mechanism to discard harmful molecules such as oxidized proteins, mtDNA, phospholipids and ROS production systems [43–46]. In our present work, NADPH oxidase, an enzyme that produces the free radical superoxide anion, was shown, for the first time in hepatocyte-derived EVs, to be more strongly expressed when producer hepatocytes exhibited an oxidative stress.
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2020, Fish and Shellfish ImmunologyCitation Excerpt :It is for example linked to autoimmune and neurodegenerative diseases and cancer [143–145], as well as playing important roles in cellular homeostasis by regulation of autophagy, cellular stress and damage [146]. Furthermore, both deimination and ubiquination have been associated with EV biology [23,147]. In Crustacea, ubiquitin mediated pathways have been studied in relation to viral infections [148] as well as other immune and anti-pathogenic responses [149], metabolism [150,224] including during molting in lobster [151].
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2020, Free Radical Biology and MedicineCitation Excerpt :This could be used for the discovery of new biomarkers of oxidative stress-related diseases [14]. Free radicals act as second messengers and an excess of ROS can affect cell signaling network and EVs biology, as redox modifications can alter both the number and cargo of EVs released by cells [15]. During pro-inflammatory and pro-oxidant conditions, that usually accompanies age, the release of EVs is induced.