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Extracellular vesicles round off communication in the nervous system

Nature Reviews Neuroscience volume 17, pages 160–172 (2016)Cite this article

Subjects

Key Points

  • The role of extracellular vesicles (EVs) in the nervous system is just beginning to be understood, but has been substantiated both in cell culture and in vivo. Major challenges in this young field include the establishment of a unified nomenclature for EVs and unified methods for their isolation, as well as the transition from studies in cell culture to those documenting their function in healthy and diseased organisms, a feat that is beginning to be achieved in invertebrate models.

  • The release and uptake of EVs in the nervous system by neurons and glial cells provide a novel mechanism of transcellular communication. Indeed, EVs are utilized for the transcellular transport of proteins, enzymes, lipids and RNA, thus influencing the physiology of the receiving cell. Neurons and glia also use EVs as a mechanism to regulate intracellular protein and RNA levels and for protein quality control.

  • Neurons can release EVs both in vivo and in cell culture, and this release is often regulated by depolarization or by agents that increase neuronal excitability. In turn, the release of EVs by glial subpopulations sometimes requires neuronal excitation.

  • Glial cells utilize EVs to regulate differentiation, myelin sheath formation and repair after injury. EVs also serve to propagate inflammatory signals in response to tissue damage and disease.

  • A role for EVs during communication in the nervous system of intact organisms has been demonstrated at the Drosophila melanogaster neuromuscular junction (NMJ) and in Caenorhabditis elegans sensory neurons. At the D. melanogaster NMJ, EVs are used to convey Wnt signals from neurons to muscles, and in C. elegans, such vesicles are used to transmit behaviourally relevant signals between organisms.

  • EVs are emerging as potent participants in the progression of disease, serving as vehicles to spread misfolded proteins in a prion-like fashion, transmitting tumorigenic activity and communicating neuroinflammation. Concomitantly, because of their unique properties, EVs are being explored as shuttles to target therapies.

Abstract

Functional neural competence and integrity require interactive exchanges among sensory and motor neurons, interneurons and glial cells. Recent studies have attributed some of the tasks needed for these exchanges to extracellular vesicles (such as exosomes and microvesicles), which are most prominently involved in shuttling reciprocal signals between myelinating glia and neurons, thus promoting neuronal survival, the immune response mediated by microglia, and synapse assembly and plasticity. Such vesicles have also been identified as important factors in the spread of neurodegenerative disorders and brain cancer. These extracellular vesicle functions add a previously unrecognized level of complexity to transcellular interactions within the nervous system.

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Figure 1: Extracellular vesicle formation and release.
Figure 2: Release of Evi-containing exosomes at the Drosophila melanogaster neuromuscular junction.

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Acknowledgements

V.B. is supported by a US National Institutes of Health grant (R37 MH070000).

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Authors and Affiliations

  1. Department of Neurobiology, University of Massachusetts Medical School, 364 Plantation Street, Worcester, 01605, Massachusetts, USA

    Vivian Budnik, Catalina Ruiz-Cañada & Franz Wendler

Authors
  1. Vivian Budnik
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  2. Catalina Ruiz-Cañada
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  3. Franz Wendler
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Corresponding author

Correspondence to Vivian Budnik.

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The authors declare no competing financial interests.

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EVpedia

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Glossary

Protein processing

Protein processing may involve protein folding, covalent modifications (for example, phosphorylation and acetylation) and/or cleavage of the protein product into a smaller biologically active protein.

Reactive microglia

In the injured or disease brain, glia can become reactive by proliferating and upregulating a number of cytoskeletal components, leading to the formation of glial scars, which replace the damaged brain cells.

Transforming proteins

Proteins that cause a cell to be transformed into a neoplastic cell, which undergoes uncontrolled cell division.

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Budnik, V., Ruiz-Cañada, C. & Wendler, F. Extracellular vesicles round off communication in the nervous system. Nat Rev Neurosci 17, 160–172 (2016). https://doi.org/10.1038/nrn.2015.29

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