Emerging Roles of Neuronal Extracellular Vesicles at the Synapse

Abstract

Extracellular vesicles (EVs) are secreted from most, if not all, cell types and are implicated in short- and long-distance signaling throughout the body. EVs are also secreted from neurons and represent an emergent neuronal communication platform. Understanding the functional implications of EV signaling to recipient neurons and glia requires understanding the cell biology involved in EV biogenesis, cargo loading, secretion, uptake, and signal transduction in the recipient cell. Here we review these major questions of EV biology while highlighting recent new insights and examples within the nervous system, such as modulating synaptic function or morphogenesis in recipient neurons.

Specific Extracellular Vesicles, Generated and Operating at Synapses, Contribute to Neuronal Effects and Signaling

“…The present, comprehensive short review illustrates the neuronal EVs generated and active at pre-synaptic terminals. These neuronal EVs, identified about 15 years ago [21,22], have been investigated from 2021 [18][19][20][23][24][25] up to now [26][27][28][29][30][31][32]. The EVs generated at synapses appear different from those generated in other neuronal areas.…”

“…In particular, EVs derived from neurons have been confirmed to exhibit components such as synaptic proteins, lipids and RNAs. Their induced generation of dendritic spines depends on relevant signals such as those induced by TrkB, with trophic effects in the spotlight for synaptic plasticity modulation [26,27]. Such inter-neuronal signaling is able to connect pre-and post-synaptic neuronal sites by the diffusion of small EVs, i.e., by the variety of signaling molecules contained in the EV vesicle cargoes.…”