Role of ATP in Extracellular Vesicle Biogenesis and Dynamics.

Marta Lombardi,Elena Adinolfi,Claudia Verderio,Martina Gabrielli

doi:10.3389/fphar.2021.654023

Marta Lombardi, Elena Adinolfi + Show 2 more

Open Access

https://doi.org/10.3389/fphar.2021.654023

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Abstract

Adenosine triphosphate (ATP) is among the molecules involved in the immune response. It acts as danger signal that promotes inflammation by activating both P2X and P2Y purinergic receptors expressed in immune cells, including microglia, and tumor cells. One of the most important receptors implicated in ATP-induced inflammation is P2X7 receptor (P2X7R). The stimulation of P2X7R by high concentration of ATP results in cell proliferation, inflammasome activation and shedding of extracellular vesicles (EVs). EVs are membrane structures released by all cells, which contain a selection of donor cell components, including proteins, lipids, RNA and ATP itself, and are able to transfer these molecules to target cells. ATP stimulation not only promotes EV production from microglia but also influences EV composition and signaling to the environment. In the present review, we will discuss the current knowledge on the role of ATP in the biogenesis and dynamics of EVs, which exert important functions in physiology and pathophysiology.

Highlights

Adenosine triphosphate (ATP) is a ubiquitous nucleotide that provides energy source within cells but acts as transmitter/signaling molecule mediating interactions among various cell types in the brain (Inoue, 2002; Hansson and Ronnback, 2003) and many other organs and systems.Under physiological conditions, the concentration of extracellular ATP is very low (400–1,000 nM), allowing a 106-fold gradient for ATP efflux (Trautmann, 2009)
P2X receptors (P2XR) are Ca2+permeable, non-selective cation channels sensitive to micromolar concentration of extracellular ATP (eATP) (Trautmann, 2009). Both P2Y receptors (P2YR) and P2XR are expressed on microglia, the immune cells resident in the brain, along with receptors specific for the ATP metabolite Adenosine, and are necessary for the rapid microglial response to changes in brain homeostasis (Orr et al, 2009; Illes et al, 2020)
The present review focuses on the role of ATP/P2X7 receptor (P2X7R) signaling axis in inducing extracellular vesicles (EVs) shedding from immune and tumor cells, and on ATP involvement in the control of EV composition and dynamics of interaction with target cells

Summary

Role of ATP in Extracellular Vesicle Biogenesis and Dynamics

Edited by: Francesco Caciagli, University of Studies G.d’Annunzio Chieti and Pescara, Italy. It acts as danger signal that promotes inflammation by activating both P2X and P2Y purinergic receptors expressed in immune cells, including microglia, and tumor cells. One of the most important receptors implicated in ATP-induced inflammation is P2X7 receptor (P2X7R). The stimulation of P2X7R by high concentration of ATP results in cell proliferation, inflammasome activation and shedding of extracellular vesicles (EVs). EVs are membrane structures released by all cells, which contain a selection of donor cell components, including proteins, lipids, RNA and ATP itself, and are able to transfer these molecules to target cells. ATP stimulation promotes EV production from microglia and influences EV composition and signaling to the environment. We will discuss the current knowledge on the role of ATP in the biogenesis and dynamics of EVs, which exert important functions in physiology and pathophysiology

INTRODUCTION

ATP STIMULATION INFLUENCES EV COMPOSITION

ATP IS AMONG THE CARGO OF EVS

CONCLUSION