Role of exosomes in neuronal development

Abstract

Neurons communicate with each other at synapses via transmission of signals from the presynaptic axon terminal to the postsynaptic site. Dendritic spines are actin-rich structures at the postsynaptic sites of most excitatory synapses in the central nervous system. The precursors of dendritic spines are long actin-rich protrusions called filopodia, which are involved in activity dependent synaptogenesis. So far, many intracellular factors that regulate filopodia formation have been identified. However, extracellular mechanisms of filopodia formation are largely unknown. In recent years, there has been growing interest in the field of extracellular vesicle (EV) research due to accumulating evidence indicating their role in cellular communication. Neuron-derived small extracellular vesicles (SEVs)/exosomes were identified to regulate filopodia formation in primary neuron cultures. Quantitative proteomics analysis revealed presence of thrombospondin type 1 containing 7a (THSD7A) in neuronal exosomes responsible for inducing filopodia. By contrast, astrocyte-derived SEVs were identified to increase dendritic spine and synapse formation. In ADSEVs, the ECM protein, fibulin-2, was found to enhance synaptogenesis by activating TGF-b signaling. In summary, EV-associated unique cargo proteins, THSD7A and fibulin-2, were found to regulate filopodia and spine formation, respectively.