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

Role of exosomes as a novel way of interneuronal communication

Les exosomes sont des vésicules d’origine endosomale sécrétées par les cellules dans leur environnement après fusion à la membrane plasmique des endosomes multivésiculés. Les exosomes représentent un nouveau mode de communication entre les cellules en permettant un transfert direct de protéines, de lipides et d’ARN. L’objectif de ma thèse était d’étudier le rôle des exosomes dans la communication entre les neurones. Précédemment, le laboratoire a montré que les neurones sécrètent des exosomes de manière régulée par l’activité synaptique. Nous avons observé que les exosomes neuronaux ne sont endocytés que par les neurones. Après avoir montré qu’ils ne contiennent que des ARN courts, nous avons réalisé un séquençage complet de leurs microARN et observé que ces microARN étaient sélectivement exportés dans les exosomes. Nos observations suggèrent que les microARN contenus dans les exosomes peuvent modifier la physiologie des neurones receveurs. Nos résultats renforcent l’hypothèse du rôle des exosomes dans la communication entre les neurones via le transfert de microARN.Exosomes are vesicles of endocytic origin released by cells into their environment following fusion of multivesicular endosomes with the plasma membrane. Exosomes represent a novel mechanism of cell communication allowing direct transfer of proteins, lipids and RNA. The goal of my PhD thesis was to study that exosomes represent a novel way of interneuronal communication. Our team has previously reported that neurons release exosomes in a way tightly regulated by synaptic activity. We observed that exosomes released by neurons are only endocytosed by neurons. We found that exosomes contain only small RNA and did a deep sequencing of all their microRNA. MicroRNA are selectively exported into exosomes. It seems that exosomal microRNA can modify the physiology of receiving neurons. Our results strengthen the hypothesis of the role of exosomes in the interneuronal communication by the way of microARN transfert

Rôle des exosomes comme nouvelle voie de communication entre les neurones

Exosomes are vesicles of endocytic origin released by cells into their environment following fusion of multivesicular endosomes with the plasma membrane. Exosomes represent a novel mechanism of cell communication allowing direct transfer of proteins, lipids and RNA. The goal of my PhD thesis was to study that exosomes represent a novel way of interneuronal communication. Our team has previously reported that neurons release exosomes in a way tightly regulated by synaptic activity. We observed that exosomes released by neurons are only endocytosed by neurons. We found that exosomes contain only small RNA and did a deep sequencing of all their microRNA. MicroRNA are selectively exported into exosomes. It seems that exosomal microRNA can modify the physiology of receiving neurons. Our results strengthen the hypothesis of the role of exosomes in the interneuronal communication by the way of microARN transfert.Les exosomes sont des vésicules d’origine endosomale sécrétées par les cellules dans leur environnement après fusion à la membrane plasmique des endosomes multivésiculés. Les exosomes représentent un nouveau mode de communication entre les cellules en permettant un transfert direct de protéines, de lipides et d’ARN. L’objectif de ma thèse était d’étudier le rôle des exosomes dans la communication entre les neurones. Précédemment, le laboratoire a montré que les neurones sécrètent des exosomes de manière régulée par l’activité synaptique. Nous avons observé que les exosomes neuronaux ne sont endocytés que par les neurones. Après avoir montré qu’ils ne contiennent que des ARN courts, nous avons réalisé un séquençage complet de leurs microARN et observé que ces microARN étaient sélectivement exportés dans les exosomes. Nos observations suggèrent que les microARN contenus dans les exosomes peuvent modifier la physiologie des neurones receveurs. Nos résultats renforcent l’hypothèse du rôle des exosomes dans la communication entre les neurones via le transfert de microARN

Exosomes as a novel way of interneuronal communication.

International audienceExosomes are small extracellular vesicles which stem from endosomes fusing with the plasma membrane; they contain lipids, proteins and RNAs that are able to modify receiving cells. Functioning of the brain relies on synapses, and certain patterns of synaptic activity can change the strength of responses at sparse groups of synapses, to modulate circuits underlying associations and memory. These local changes of the synaptic physiology in one neuron driven by another have, so far, been explained by classical signal transduction modulating transcription, translation and post-translational modifications. We have accumulated in vitro evidence that exosomes released by neurons in a way depending on synaptic activity can be recaptured by other neurons. Some lipids, proteins and RNAs contained in exosomes secreted by emitting neurons could directly modify signal transduction and protein expression in receiving cells. Exosomes may be an ideal mechanism for anterograde and retrograde information transfer across synapses underlying local changes in synaptic plasticity. Exosomes might also participate in the spreading across the nervous system of pathological proteins such as PrPSc (abnormal disease-specific conformation of prion protein), APP (amyloid precursor protein) fragments, phosphorylated tau or α-synuclein

The JAK/STAT Pathway Is Involved in Synaptic Plasticity

The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is involved in many cellular processes, including cell growth and differentiation, immune functions and cancer. It is activated by various cytokines, growth factors, and protein tyrosine kinases (PTKs) and regulates the transcription of many genes. Of the four JAK isoforms and seven STAT isoforms known, JAK2 and STAT3 are highly expressed in the brain where they are present in the postsynaptic density (PSD). Here, we demonstrate a new neuronal function for the JAK/STAT pathway. Using a variety of complementary approaches, we show that the JAK/STAT pathway plays an essential role in the induction of NMDA-receptor dependent long-term depression (NMDAR-LTD) in the hippocampus. Therefore, in addition to established roles in cytokine signaling, the JAK/STAT pathway is involved in synaptic plasticity in the brain