Release of exosomes from differentiated neurons and its regulation by synaptic glutamatergic activity

被引:442
作者
Lachenal, Gaelle [1 ,2 ]
Pernet-Gallay, Karin [1 ,3 ]
Chivet, Mathilde [1 ,2 ]
Hemming, Fiona J. [1 ,2 ]
Belly, Agnes [1 ,2 ]
Bodon, Gilles [1 ,2 ]
Blot, Beatrice [1 ,2 ]
Haase, Georg [4 ,5 ]
Goldberg, Yves [1 ,2 ]
Sadoul, Remy [1 ,2 ]
机构
[1] Univ Grenoble 1, Grenoble Inst Neurosci, F-38042 Grenoble, France
[2] INSERM, U836, Equipe 2, F-38042 Grenoble, France
[3] INSERM, U836, Equipe 1, F-38042 Grenoble, France
[4] CNRS, F-13402 Marseille, France
[5] Univ Mediterranee, UMR 6196, F-13402 Marseille, France
关键词
Exosomes; Multivesicular bodies; Tetanus toxin; Synaptic activity; TETANUS TOXIN; MULTIVESICULAR BODIES; PROTEINS; RECEPTOR; ACTIVATION; SECRETION; CARDIOTROPHIN-1; INFLAMMASOME; EXOCYTOSIS; MECHANISM;
D O I
10.1016/j.mcn.2010.11.004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Exosomes are microvesicles released into the extracellular medium upon fusion to the plasma membrane of endosomal intermediates called multivesicular bodies. They represent ways for discarding proteins and metabolites and also for intercellular transfer of proteins and RNAs. In the nervous system, it has been hypothesized that exosomes might be involved in the normal physiology of the synapse and possibly allow the trans-synaptic propagation of pathogenic proteins throughout the tissue. As a first step to validate this concept, we used biochemical and morphological approaches to demonstrate that mature cortical neurons in culture do indeed secrete exosomes. Using electron microscopy, we observed exosomes being released from somato-dendritic compartments. The endosomal origin of exosomes was demonstrated by showing that the C-terminal domain of tetanus toxin specifically endocytosed by neurons and accumulating inside multivesicular bodies, is released in the extracellular medium in association with exosomes. Finally, we found that exosomal release is modulated by glutamatergic synaptic activity, suggesting that this process might be part of normal synaptic physiology. Thus, our study paves the way towards the demonstration that exosomes take part in the physiology of the normal and pathological nervous system. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码:409 / 418
页数:10
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