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ATP Modifies the Proteome of Extracellular Vesicles Released by Microglia and Influences Their Action on Astrocytes

Francesco Drago1,2, Marta Lombardi3, Ilaria Prada4

  • 1Univ. Lille, INSERM, U1192 - Protéomique Réponse Inflammatoire Spectrométrie de Masse - PRISM, Lille, France.

Frontiers in Pharmacology
|January 12, 2018
PubMed

Insights

Extracellular ATP stimulates microglia to release extracellular vesicles (EVs) containing proteins involved in cell adhesion and metabolism. These ATP-stimulated EVs may alter astrocyte responses, revealing new signaling mechanisms.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Biochemistry

Background:

  • Extracellular ATP (adenosine triphosphate) activates microglia, a key immune cell in the brain.
  • Microglia release extracellular vesicles (EVs), which mediate intercellular communication.
  • Previous work demonstrated that ATP-stimulated EVs (ATP-EVs) induce neuroinflammation in vitro and in vivo.

Purpose of the Study:

  • To elucidate the proteome of EVs released by microglia upon ATP stimulation.
  • To identify proteins sorted into EVs during microglia activation.
  • To understand how these proteins may influence recipient cells, particularly astrocytes.

Main Methods:

  • Label-free quantitative proteomic analysis.
  • Characterization of EVs released constitutively versus those released upon ATP stimulation.
  • Comparative proteomic profiling of microglia-derived EVs.

Main Results:

  • ATP stimulation alters the protein cargo of microglia-derived EVs.
  • Specific proteins involved in cell adhesion, extracellular matrix organization, autophagy-lysosomal pathways, and cellular metabolism are enriched in ATP-EVs.
  • These findings suggest a mechanism for microglia-astrocyte communication.

Conclusions:

  • ATP-induced microglia activation leads to the release of EVs with a distinct proteomic profile.
  • The identified proteins in ATP-EVs offer insights into molecular mechanisms of microglia response and signaling.
  • This study provides a foundation for understanding how microglia EVs modulate the brain microenvironment.
Keywords:
ATPastrocyte activationextracellular vesiclesmicrogliaproteomics

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