Release of exosomes from differentiated neurons and its regulation by synaptic glutamatergic activity
Release of exosomes from differentiated neurons and its regulation by synaptic glutamatergic activity
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DOI：
10.1016/j.mcn.2010.11.004
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发表时间：
2011-02-01
影响因子：
3.5
通讯作者：
Sadoul, Remy
中科院分区：
文献类型：
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作者：
Lachenal, Gaelle;Pernet-Gallay, Karin;Sadoul, Remy
外泌体是在融合到称为多泡体的内体中间体的质膜后释放到细胞外介质中的微泡。它们代表了丢弃蛋白质和代谢物的方式，也代表了蛋白质和RNA的细胞间转移。在神经系统中，已经假设外泌体可能参与突触的正常生理学，并且可能允许致病蛋白在整个组织中的跨突触传播。作为验证这一概念的第一步，我们使用生物化学和形态学方法来证明培养中的成熟皮层神经元确实分泌外泌体。使用电子显微镜，我们观察到外泌体被释放的体细胞-树突状隔室。外泌体的内体起源通过显示破伤风毒素的C-末端结构域特异性地被神经元内吞并在多泡体内积累而被释放到与外泌体相关的细胞外介质中来证明。最后，我们发现外泌体的释放是由突触能活动调节的，这表明这一过程可能是正常突触生理的一部分。因此，我们的研究为证明外泌体参与正常和病理神经系统的生理学铺平了道路。(C)2010年爱思唯尔公司All rights reserved.
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.