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Open Access Highly Accessed Research article

Wnt3a induces exosome secretion from primary cultured rat microglia

Claudie Hooper1*, Ricardo Sainz-Fuertes1, Steven Lynham1, Abdul Hye1, Richard Killick1, Alice Warley2, Cecilia Bolondi1, Jennifer Pocock3 and Simon Lovestone1

Author Affiliations

1 King’s College London, MRC Centre for Neurodegenerative Research, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE5 8AF, UK

2 Centre for Ultrastructural Imaging, King’s College London, New Hunts House, Guy’s Campus, London, SE1 1UL, UK

3 Cell Signalling laboratory, Institute of Neurology, University College London, 1 Wakefield Street, London, WC1N 1PJ, UK

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BMC Neuroscience 2012, 13:144  doi:10.1186/1471-2202-13-144

Published: 23 November 2012

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 β-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.

Keywords:
Wnt3a; Glycogen synthase kinase; Microglia; Exosomes; Signaling; Proteomic