Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate

Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate
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DOI:
10.1038/nn1246
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发表时间:
2004-06-01
影响因子:
25
通讯作者:
Volterra, A
Volterra, A
中科院分区:
医学1区
文献类型:
--
作者:
Bezzi, P;Gundersen, V;Volterra, A

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星形胶质细胞通过释放化学递质建立快速的细胞间通讯。然而,这种释放的潜在机制和功能意义尚不清楚。在这里,我们确定了一个星形胶质细胞囊泡室,是谷氨酸胞吐。使用postembedding免疫金标记的大鼠海马,我们表明,囊泡谷氨酸转运蛋白(VGLUT 1/2)和囊泡陷阱蛋白,cellubrevin,都在小泡状细胞器中表达,类似于突触囊泡的mammatergic终端。星形胶质细胞囊泡,这是不密集的,因为他们的神经元对应物,可以观察到在小团体在网站附近的神经元结构轴承谷氨酸受体。用全内反射荧光(TIRF)显微镜在活的星形胶质细胞中动态研究了标记的含VGLUT的囊泡。代谢型谷氨酸受体激活后,星形胶质细胞囊泡进行快速(毫秒)的Ca 2+和SNARE依赖的胞吐融合,伴随着谷氨酸的释放。这些数据证明了神经胶质细胞中存在Ca 2+依赖的谷氨酸量子释放活性,这在以前被认为是特异于突触的。
Astrocytes establish rapid cell-to-cell communication through the release of chemical transmitters. The underlying mechanisms and functional significance of this release are, however, not well understood. Here we identify an astrocytic vesicular compartment that is competent for glutamate exocytosis. Using postembedding immunogold labeling of the rat hippocampus, we show that vesicular glutamate transporters (VGLUT1/2) and the vesicular SNARE protein, cellubrevin, are both expressed in small vesicular organelles that resemble synaptic vesicles of glutamatergic terminals. Astrocytic vesicles, which are not as densely packed as their neuronal counterparts, can be observed in small groups at sites adjacent to neuronal structures bearing glutamate receptors. Fluorescently tagged VGLUT-containing vesicles were studied dynamically in living astrocytes by total internal reflection fluorescence (TIRF) microscopy. After activation of metabotropic glutamate receptors, astrocytic vesicles underwent rapid (milliseconds) Ca2+- and SNARE-dependent exocytic fusion that was accompanied by glutamate release. These data document the existence of a Ca2+-dependent quantal glutamate release activity in glia that was previously considered to be specific to synapses.