Extracellular vesicles and intercellular communication within the nervous system
Valentina Zappulli, Kristina Pagh Friis, Zachary Fitzpatrick, Casey A. Maguire, Xandra O. Breakefield
Valentina Zappulli, Kristina Pagh Friis, Zachary Fitzpatrick, Casey A. Maguire, Xandra O. Breakefield
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Review Series

Extracellular vesicles and intercellular communication within the nervous system

Abstract

Extracellular vesicles (EVs, including exosomes) are implicated in many aspects of nervous system development and function, including regulation of synaptic communication, synaptic strength, and nerve regeneration. They mediate the transfer of packets of information in the form of nonsecreted proteins and DNA/RNA protected within a membrane compartment. EVs are essential for the packaging and transport of many cell-fate proteins during development as well as many neurotoxic misfolded proteins during pathogenesis. This form of communication provides another dimension of cellular crosstalk, with the ability to assemble a “kit” of directional instructions made up of different molecular entities and address it to specific recipient cells. This multidimensional form of communication has special significance in the nervous system. How EVs help to orchestrate the wiring of the brain while allowing for plasticity associated with learning and memory and contribute to regeneration and degeneration are all under investigation. Because they carry specific disease-related RNAs and proteins, practical applications of EVs include potential uses as biomarkers and therapeutics. This Review describes our current understanding of EVs and serves as a springboard for future advances, which may reveal new important mechanisms by which EVs in coordinate brain and body function and dysfunction.

Authors

Valentina Zappulli, Kristina Pagh Friis, Zachary Fitzpatrick, Casey A. Maguire, Xandra O. Breakefield

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Figure 3

Vesicular exchange in the brain tumor microenvironment.

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Vesicular exchange in the brain tumor microenvironment. GBM tumors are m...
GBM tumors are made up of a heterogeneous group of genetically related cancer cells, shown here as two types of differentiated tumor cells (DTCs) within the same tumor. Tumors also contain glioma stem cells (GSCs), which tend to be resistant to therapy and are thought to rejuvenate differentiated tumor cells after therapy. Tumor cells release at least three types of vesicles — exosomes, microvesicles, and large oncosomes. Normal cells in the brain tumor environment include T cells, microglia, macrophages, and endothelial cells, which also release exosomes and microvesicles. The secretome and EVs of the tumors modulate the phenotype of these normal cells, including promoting an immune-repressive T cell Th2 phenotype, stimulating microglia and macrophages to assume the M2-activated state in support of tumor progression, and inducing endothelial cell–mediated angiogenesis as well as opening up the extracellular matrix (ECM) to facilitate invasion of cancer cells. Vesicles, shown with color coding that matches the cell of origin, are exchanged among all cells in the environment. They all contain a cell-specific cargo of lipids, proteins, and nucleic acids, which are delivered into recipient cells.