Exosomes secreted by cortical neurons upon glutamatergic synapse activation specifically interact with neurons.
Exosomes are nano-sized vesicles of endocytic origin released into the extracellular space upon fusion of multivesicular bodies with the plasma membrane. Exosomes represent a novel mechanism of cell-cell communication allowing direct transfer of proteins, lipids and RNAs. In the nervous system, both glial and neuronal cells secrete exosomes in a way regulated by glutamate. It has been hypothesized that exosomes can be used for interneuronal communication implying that neuronal exosomes should bind to other neurons with some kind of specificity. Here, dissociated hippocampal cells were used to compare the specificity of binding of exosomes secreted by neuroblastoma cells to that of exosomes secreted by cortical neurons. We found that exosomes from neuroblastoma cells bind indiscriminately to neurons and glial cells and could be endocytosed preferentially by glial cells. In contrast, exosomes secreted from stimulated cortical neurons bound to and were endocytosed only by neurons. Thus, our results demonstrate for the first time that exosomes released upon synaptic activation do not bind to glial cells but selectively to other neurons suggesting that they can underlie a novel aspect of interneuronal communication.
Institut National de la Santé et de la Recherche Médicale (INSERM), U836, Grenoble, France; Grenoble Institute of Neuroscience, University of Grenoble Alpes, Grenoble, France.
Mathilde
M
Chivet
Institut National de la Santé et de la Recherche Médicale (INSERM), U836, Grenoble, France; Grenoble Institute of Neuroscience, University of Grenoble Alpes, Grenoble, France.
Charlotte
C
Javalet
Institut National de la Santé et de la Recherche Médicale (INSERM), U836, Grenoble, France; Grenoble Institute of Neuroscience, University of Grenoble Alpes, Grenoble, France.
Karine
K
Laulagnier
Institut National de la Santé et de la Recherche Médicale (INSERM), U836, Grenoble, France; Grenoble Institute of Neuroscience, University of Grenoble Alpes, Grenoble, France.
Béatrice
B
Blot
Institut National de la Santé et de la Recherche Médicale (INSERM), U836, Grenoble, France; Grenoble Institute of Neuroscience, University of Grenoble Alpes, Grenoble, France.
Fiona J
FJ
Hemming
Institut National de la Santé et de la Recherche Médicale (INSERM), U836, Grenoble, France; Grenoble Institute of Neuroscience, University of Grenoble Alpes, Grenoble, France; remy.sadoul@ujf-grenoble.fr.
Rémy
R
Sadoul
CD63 tetraspanin; central nervous system; exosomes; extracellular vesicles; intercellular communication; multivesicular bodies; neurons; tetanus toxin