Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication.
Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication.
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DOI：
10.1371/journal.pbio.1001604
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发表时间：
2013-07
期刊：
影响因子：
9.8
通讯作者：
Krämer-Albers EM
中科院分区：
文献类型：
--
作者：
Frühbeis C;Fröhlich D;Kuo WP;Amphornrat J;Thilemann S;Saab AS;Kirchhoff F;Möbius W;Goebbels S;Nave KA;Schneider A;Simons M;Klugmann M;Trotter J;Krämer-Albers EM
神经元活性激发髓鞘形成的少突胶质细胞通过刺激离子型谷氨酸受体释放外泌体，并且一旦释放，这些囊泡被传递神经保护的神经元内化。神经元和少突胶质细胞之间的相互作用不仅对髓鞘形成至关重要，而且对轴突的长期存活也至关重要。轴突的变性发生在几种人类髓鞘疾病中，然而维持轴突完整性的轴突-胶质细胞通讯的分子机制知之甚少。在这里，我们描述了信号介导的外泌体从少突胶质细胞转移到神经元。这些内体衍生的囊泡由少突胶质细胞分泌，并携带特定的蛋白质和RNA货物。我们发现，神经递质谷氨酸的活性依赖性释放触发少突胶质细胞外泌体分泌介导的Ca 2+进入通过少突胶质细胞NMDA和AMPA受体。反过来，神经元通过内吞作用内化释放的外泌体。将少突胶质细胞衍生的外泌体注射到小鼠脑中导致神经元中外泌体货物的功能恢复。向培养的神经元供应少突胶质细胞外泌体改善了细胞应激条件下的神经元活力。这些发现表明，少突胶质细胞外泌体参与了一种新的双向神经元-胶质细胞通信模式，有助于神经元的完整性。脑功能在很大程度上取决于电兴奋神经元和周围神经胶质细胞之间的通信。髓鞘生成少突胶质细胞是一种脑细胞，隔离主要的神经元过程（轴突），并有助于可持续地维持轴突健康，这在分子方面知之甚少。几种细胞类型释放称为外泌体的微泡，其包含遗传信息（主要是RNA），并且可以充当将特定货物转移到靶细胞的载体。在这里，我们证明了少突胶质细胞分泌的外泌体响应神经元信号进入神经元，使其货物功能可用于神经元代谢。我们在培养的细胞中发现，少突胶质细胞的外泌体释放是由神经递质谷氨酸通过激活离子型谷氨酸受体触发的。我们还表明，神经胶质细胞外泌体通过内吞途径被神经元内化。通过用报告酶修饰少突胶质细胞外泌体，我们可以证明外泌体货物在培养物中以及在将外泌体注射到小鼠脑中后在体内被靶神经元回收。当用少突胶质细胞外泌体处理时，用应激生长条件挑战的神经元受到保护。该研究引入了神经系统中相互细胞通讯的新概念，并确定了信号介导的外泌体从少突胶质细胞到神经元的转移有助于维护轴突健康。
Neuronal activity provokes myelinating oligodendrocytes to release exosomes by stimulation of ionotropic glutamate receptors, and that once released, these vesicles are internalized by neurons conveying neuroprotection. Reciprocal interactions between neurons and oligodendrocytes are not only crucial for myelination, but also for long-term survival of axons. Degeneration of axons occurs in several human myelin diseases, however the molecular mechanisms of axon-glia communication maintaining axon integrity are poorly understood. Here, we describe the signal-mediated transfer of exosomes from oligodendrocytes to neurons. These endosome-derived vesicles are secreted by oligodendrocytes and carry specific protein and RNA cargo. We show that activity-dependent release of the neurotransmitter glutamate triggers oligodendroglial exosome secretion mediated by Ca2+ entry through oligodendroglial NMDA and AMPA receptors. In turn, neurons internalize the released exosomes by endocytosis. Injection of oligodendroglia-derived exosomes into the mouse brain results in functional retrieval of exosome cargo in neurons. Supply of cultured neurons with oligodendroglial exosomes improves neuronal viability under conditions of cell stress. These findings indicate that oligodendroglial exosomes participate in a novel mode of bidirectional neuron-glia communication contributing to neuronal integrity. Brain function largely depends on the communication between electrically excitable neurons and surrounding glial cells. Myelinating oligodendrocytes are a type of brain cell that insulate major neuronal processes (axons) and help to sustainably maintain axonal health, which is poorly understood in molecular terms. Several cell types release microvesicles termed exosomes that include genetic information (primarily RNA) and can act as vehicles transferring specific cargo to target cells. Here, we demonstrate that exosomes secreted by oligodendrocytes in response to neuronal signals enter neurons to make their cargo functionally available to the neuronal metabolism. We revealed in cultured cells that exosome release from oligodendrocytes is triggered by the neurotransmitter glutamate through activation of ionotropic glutamate receptors. We also show that glial exosomes are internalized by neurons via an endocytic pathway. By modifying oligodendroglial exosomes with a reporter enzyme, we could demonstrate that the exosome cargo is recovered by target neurons in culture as well as in vivo after injection of exosomes into the mouse brain. Neurons challenged with stressful growth conditions were protected when treated with oligodendroglial exosomes. The study introduces a new concept of reciprocal cell communication in the nervous system and identifies the signal-mediated transfer of exosomes from oligodendrocytes to neurons contributing to the preservation of axonal health.
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影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
DOI：
10.1523/jneurosci.2455-11.2011
发表时间：
2011-08-31
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
De Biase LM;Kang SH;Baxi EG;Fukaya M;Pucak ML;Mishina M;Calabresi PA;Bergles DE
通讯作者：
Bergles DE
影响因子：
4
作者：
Chivet M;Hemming F;Pernet-Gallay K;Fraboulet S;Sadoul R
通讯作者：
Sadoul R
影响因子：
64.8
作者：
Bergles, DE;Roberts, JDB;Jahr, CE
通讯作者：
Jahr, CE
DOI：
10.1196/annals.1391.032
发表时间：
2007-01-01
期刊：
STRESS RESPONSES IN BIOLOGY AND MEDICINE
影响因子：
--
作者：
Brown, Ian R.
通讯作者：
Brown, Ian R.