TY - JOUR
T1 - ATP modifies the proteome of extracellular vesicles released by microglia and influences their action on astrocytes
AU - Drago, Francesco
AU - Lombardi, Marta
AU - Prada, Ilaria
AU - Gabrielli, Martina
AU - Joshi, Pooja
AU - Cojoc, Dan
AU - Franck, Julien
AU - Fournier, Isabelle
AU - Vizioli, Jacopo
AU - Verderio, Claudia
PY - 2017/12/13
Y1 - 2017/12/13
N2 - Extracellular ATP is among molecules promoting microglia activation and inducing the release of extracellular vesicles (EVs), which are potent mediators of intercellular communication between microglia and the microenvironment. We previously showed that EVs produced under ATP stimulation (ATP-EVs) propagate a robust inflammatory reaction among astrocytes and microglia in vitro and in mice with subclinical neuroinflammation (Verderio et al., 2012). However, the proteome of EVs released upon ATP stimulation has not yet been elucidated. In this study we applied a label free proteomic approach to characterize the proteome of EVs released constitutively and during microglia activation with ATP. We show that ATP drives sorting in EVs of a set of proteins implicated in cell adhesion/extracellular matrix organization, autophagy-lysosomal pathway and cellular metabolism, that may influence the response of recipient astrocytes to EVs. These data provide new clues to molecular mechanisms involved in microglia response to ATP and in microglia signaling to the environment via EVs.
AB - Extracellular ATP is among molecules promoting microglia activation and inducing the release of extracellular vesicles (EVs), which are potent mediators of intercellular communication between microglia and the microenvironment. We previously showed that EVs produced under ATP stimulation (ATP-EVs) propagate a robust inflammatory reaction among astrocytes and microglia in vitro and in mice with subclinical neuroinflammation (Verderio et al., 2012). However, the proteome of EVs released upon ATP stimulation has not yet been elucidated. In this study we applied a label free proteomic approach to characterize the proteome of EVs released constitutively and during microglia activation with ATP. We show that ATP drives sorting in EVs of a set of proteins implicated in cell adhesion/extracellular matrix organization, autophagy-lysosomal pathway and cellular metabolism, that may influence the response of recipient astrocytes to EVs. These data provide new clues to molecular mechanisms involved in microglia response to ATP and in microglia signaling to the environment via EVs.
KW - Astrocyte activation
KW - ATP
KW - Extracellular vesicles
KW - Microglia
KW - Proteomics
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U2 - 10.3389/fphar.2017.00910
DO - 10.3389/fphar.2017.00910
M3 - Article
AN - SCOPUS:85038239508
VL - 8
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
SN - 1663-9812
IS - DEC
M1 - 910
ER -