Exosomes secreted by cortical neurons upon glutamatergic synapse activation specifically interact with neurons.
Exosomes secreted by cortical neurons upon glutamatergic synapse activation specifically interact with neurons.
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DOI：
10.3402/jev.v3.24722
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发表时间：
2014
影响因子：
16
通讯作者：
Sadoul R
中科院分区：
文献类型：
--
作者：
Chivet M;Javalet C;Laulagnier K;Blot B;Hemming FJ;Sadoul R
外切小体是多囊泡体与质膜融合后释放到细胞外间隙的内源性纳米小泡。外切体代表了一种新的细胞间通讯机制，允许蛋白质、脂类和RNA的直接转移。在神经系统中，神经胶质细胞和神经细胞都以谷氨酸调节的方式分泌外切体。已有的假说认为，外切体可以用于神经元间的通讯，这意味着神经元外切体应该以某种特异性与其他神经元结合。在这里，我们使用分离的海马细胞来比较神经母细胞瘤细胞分泌的外切体与皮质神经元分泌的外切体结合的特异性。我们发现神经母细胞瘤细胞的外切体不分青红皂白地与神经元和神经胶质细胞结合，并可优先被神经胶质细胞内吞。相比之下，受刺激的皮质神经元分泌的外切体与神经元结合，并仅由神经元内吞。因此，我们的结果首次证明，突触激活时释放的外切体不与神经胶质细胞结合，而是选择性地与其他神经元结合，这表明它们可以为神经元间通讯的一个新方面奠定基础。
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.