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Updated: Nov 14, 2025

Characterization of Immune Cell-derived Extracellular Vesicles and Studying Functional Impact on Cell Environment
Published on: June 2, 2020
Astrocyte-derived small extracellular vesicles promote synapse formation via fibulin-2-mediated TGF-β signaling
Mikin R Patel1, Alissa M Weaver2
1Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Biological Sciences, Vanderbilt University, Nashville, TN 37232, USA.
Abstract:
Neuronal synapse formation is critical for brain development and depends on secreted factors from astrocytes. Here, we report that small extracellular vesicles (EVs) secreted from primary astrocytes, but not from neurons or C6 glioma cells, greatly enhance spine and synapse formation by primary cortical neurons. A comparative proteomics analysis of small EVs from astrocytes, neurons, and C6 glioma cells identified fibulin-2 as a promising EV cargo to regulate synaptogenesis. Treatment of cortical neurons with recombinant fibulin-2 increased the formation of spines and synapses, similar to the effect of small EVs. In addition, treatment of neurons with fibulin-2 or astrocyte-derived small EVs led to increased phosphorylation of Smad2, an indicator of TGF-β signaling. Finally, the effects of fibulin-2 and astrocyte-derived small EVs on synapse formation were reversed by inhibiting transforming growth factor β (TGF-β) signaling. These data suggest a model in which astrocyte EVs promote synapse formation via fibulin-2-mediated activation of TGF-β signaling.
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