Trafficking and fusion of neuropeptide Y-containing dense-core granules in astrocytes.

Trafficking and fusion of neuropeptide Y-containing dense-core granules in astrocytes.
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DOI:
10.1523/jneurosci.5361-07.2008
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发表时间:
2008-12-17
期刊:
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子:
--
通讯作者:
Whim MD
Whim MD
中科院分区:
其他
文献类型:
--
作者:
Ramamoorthy P;Whim MD

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越来越清楚的是,星形胶质细胞是突触功能的积极参与者,并表现出一些特性,如分泌经典的递质,以前被认为是神经元独有的。这些相似性是否延伸到神经肽的释放,另一类主要的递质还不太清楚。在这里,我们表明,皮质星形胶质细胞可以合成本地和外来的神经肽,并可以分泌它们在一个刺激依赖性的方式。RT-PCR和质谱表明,皮质星形胶质细胞含有神经肽Y,一种广泛的神经递质。免疫细胞化学研究揭示了NPY免疫反应(NPY-IR)斑点,共定位与受调节的分泌途径的标志物。这些NPY-IR点是不同的突触样囊泡,包含经典的递质和两种类型的细胞器的差异分布。在代谢型谷氨酸受体激活和钙从细胞内储存释放后,NPY-免疫斑点与细胞膜融合,并显示含肽的致密核心。为了确定随后是否发生肽分泌,从表达NPY-红色荧光蛋白的星形胶质细胞中监测胞吐作用。在活细胞中,谷氨酸受体活化后,NPY-RFP标记的斑点的强度以阶梯状方式下降,表明颗粒内容物的调节释放。由于神经肽Y是一种广泛和有效的调节突触传递,这些结果表明,星形胶质细胞可以发挥作用,在中枢神经系统中的突触信号的肽能调制。
It is becoming clear that astrocytes are active participants in synaptic functioning and exhibit properties, such as the secretion of classical transmitters, previously thought to be exclusively neuronal. Whether these similarities extend to the release of neuropeptides, the other major class of transmitters is less clear. Here we show that cortical astrocytes can synthesize both native and foreign neuropeptides and can secrete them in a stimulation-dependent manner. RT-PCR and mass spectrometry indicate that cortical astrocytes contain neuropeptide Y, a widespread neuronal transmitter. Immunocytochemical studies reveal NPY-immunoreactive (NPY-ir) puncta that co-localize with markers of the regulated secretory pathway. These NPY-ir puncta are distinct from the synaptic-like vesicles that contain classical transmitters and the two types of organelles are differentially distributed. After activation of metabotropic glutamate receptors and the release of calcium from intracellular stores, the NPY-ir puncta fuse with the cell membrane and the peptide-containing dense cores are displayed. To determine whether peptide secretion subsequently occurred, exocytosis was monitored from astrocytes expressing NPY-red fluorescent protein. In live cells, following activation of glutamate receptors, the intensity of the NPY-RFP labeled puncta declined in a step-like manner indicating a regulated release of the granular contents. Since NPY is a widespread and potent regulator of synaptic transmission, these results suggest that astrocytes could play a role in the peptidergic modulation of synaptic signaling in the CNS.
末期末期ATT20细胞中体中肾上腺皮质激素分泌颗粒的积累:分泌颗粒沿微管行进的证据。
DOI: 10.1083/jcb.104.4.1047
发表时间: 1987-04
影响因子: 7.8
作者:
Tooze, J;Burke, B
通讯作者: Burke, B