Exosome reporter mice reveal the involvement of exosomes in mediating neuron to astroglia communication in the CNS

Men, Yuqin, Julia Yelick, Shijie Jin, Yang Tian, Ming Sum R. Chiang, Haruki Higashimori, Eoin Brown, Rachel Jarvis, and Yongjie Yang. "Exosome reporter mice reveal the involvement of exosomes in mediating neuron to astroglia communication in the CNS." Nature communications 10, no. 1 (2019): 1-18.

Abstract

Astroglia play active and diverse roles in modulating neuronal/synaptic functions in the CNS. How these astroglial functions are regulated, especially by neuronal signals, remains largely unknown. Exosomes, a major type of extracellular vesicles (EVs) that originate from endosomal intraluminal vesicles (ILVs), have emerged as a new intercellular communication process. By generating cell-type-specific ILVs/exosome reporter (CD63-GFPf/f) mice and immuno-EM/confocal image analysis, we found that neuronal CD63-GFP+ ILVs are primarily localized in soma and dendrites, but not in axonal terminals in vitro and in vivo. Secreted neuronal exosomes contain a subset of microRNAs (miRs) that is distinct from the miR profile of neurons. These miRs, especially the neuron-specific miR-124-3p, are potentially internalized into astrocytes. MiR-124-3p further up-regulates the predominant glutamate transporter GLT1 by suppressing GLT1-inhibiting miRs. Our findings suggest a previously undescribed neuronal exosomal miR-mediated genetic regulation of astrocyte functions, potentially opening a new frontier in understanding CNS intercellular communication.

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