84 Citations (Scopus)

Abstract

Background: Microglia, the immune effector cells of the CNS and the signaling molecule Wnt, both play critical roles in neurodevelopment and neurological disease. Here we describe the inducible release of exosomes from primary cultured rat microglia following treatment with recombinant carrier-free Wnt3a.

Results: Wnt3a was internalised into microglia, being detectable in early endosomes, and secreted in exosomes through a GSK3-independent mechanism. Electron microscopy demonstrated that exosomes were elliptical, electron-dense (100 nm) vesicles that coalesced with time in vitro. In contrast to microglia, primary cortical neurons released exosomes constitutively and the quantity of exosomes released was not altered by Wnt3a treatment. The proteomic profile of the microglial-derived exosomes was characterised using liquid chromatography-tandem mass spectrometry (LC/MS/MS) and the vesicles were found to be associated with proteins involved in cellular architecture, metabolism, protein synthesis and protein degradation including beta-actin, glyceraldehyde-3-phosphate dehydrogenase, ribosomal subunits and ubiquitin (45 proteins in total). Unlike lipopolysaccharide, Wnt3a did not induce a neurotoxic, pro-inflammatory phenotype in primary microglia.

Conclusion: These findings reveal a novel mechanism through which Wnt3a signals in microglia resulting in the release of exosomes loaded with proteinaceous cargo.

Original languageEnglish
Article number144
Number of pages17
JournalBMC NEUROSCIENCE
Volume13
DOIs
Publication statusPublished - 23 Nov 2012

Keywords

  • BETA-CATENIN
  • ALPHA-SYNUCLEIN
  • Signaling
  • PATHWAYS
  • PROTEIN
  • MECHANISM
  • CELLS
  • Wnt3a
  • Microglia
  • MACROPHAGES
  • ALZHEIMERS-DISEASE
  • CALCIUM-DEPENDENT MANNER
  • Glycogen synthase kinase
  • BRAIN
  • Proteomic
  • Exosomes

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