Wnt3a induces exosome secretion from primary cultured rat microglia

BMC Neuroscience

Research Article

Jennifer Pocock¹  Alice Warley²  Abdul Hye³  Cecilia Bolondi³  Claudie Hooper³  Simon Lovestone³  Ricardo Sainz-Fuertes³  Steven Lynham³  Richard Killick³ 

[1] Cell Signalling laboratory, Institute of Neurology, University College London, 1 Wakefield Street, WC1N 1PJ, London, UK;Centre for Ultrastructural Imaging, King’s College London, New Hunts House, Guy’s Campus, SE1 1UL, London, UK;King’s College London, MRC Centre for Neurodegenerative Research, Institute of Psychiatry, De Crespigny Park, Denmark Hill, SE5 8AF, London, UK;

关键词: Wnt3a;    Glycogen synthase kinase;    Microglia;    Exosomes;    Signaling;    Proteomic;   

DOI  :  10.1186/1471-2202-13-144

 received in 2012-04-22, accepted in 2012-10-12,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundMicroglia, 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.ResultsWnt3a 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.ConclusionThese findings reveal a novel mechanism through which Wnt3a signals in microglia resulting in the release of exosomes loaded with proteinaceous cargo.

【 授权许可】

CC BY   
© Hooper et al.; licensee BioMed Central Ltd. 2012