Neuronal activity regulates glutamate transporter dynamics in developing astrocytes.
Neuronal activity regulates glutamate transporter dynamics in developing astrocytes.
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DOI：
10.1002/glia.21249
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发表时间：
2012-02
期刊：
影响因子：
6.2
通讯作者：
Dailey, Michael E.
中科院分区：
文献类型：
--
作者：
Benediktsson, Adrienne M.;Marrs, Glen S.;Tu, Jian Cheng;Worley, Paul F.;Roth-Stein, Jeffrey D.;Bergles, Dwight E.;Dailey, Michael E.
谷氨酸转运蛋白在CNS中维持低的谷氨酸环境水平，并在突触处形成谷氨酸受体的激活。然而，调节谷氨酸释放位点附近转运蛋白的运输和定位的机制知之甚少。在这里，我们研究了亚细胞分布和动态重塑的主要谷氨酸转运蛋白GLT-1（EAAT 2）在发展中的海马星形胶质细胞。免疫标记显示，内源性GLT-1被集中成离散的集群沿着发展的星形胶质细胞的分支，并置优先突触蛋白-1阳性突触。在星形胶质细胞中表达的GFP-GLT-1融合蛋白也形成了不同的簇，排列在星形胶质细胞突起的边缘，以及丝状伪足和棘状结构的尖端。组织切片中的延时3D共聚焦成像显示，GFP-GLT-1簇在几分钟的时间尺度上动态重塑。一些转运蛋白簇随着丝状伪足的伸展和收缩在发育中的星形胶质细胞分支内移动，而另一些转运蛋白簇则在棘状结构的尖端保持稳定的位置。用河豚毒素阻断神经元活动降低了GLT-1簇的密度和突触周围定位。相反，神经元活动的增强增加了GLT-1簇的大小及其与突触的接近程度。总之，这些发现表明，神经元活动影响谷氨酸转运蛋白在星形胶质细胞膜发育中的组织及其相对于突触的位置。
Glutamate transporters maintain a low ambient level of glutamate in the CNS and shape the activation of glutamate receptors at synapses. Nevertheless, the mechanisms that regulate the trafficking and localization of transporters near sites of glutamate release are poorly understood. Here we examined the subcellular distribution and dynamic remodeling of the predominant glutamate transporter GLT-1 (EAAT2) in developing hippocampal astrocytes. Immunolabeling revealed that endogenous GLT-1 is concentrated into discrete clusters along branches of developing astrocytes that were apposed preferentially to synapsin-1 positive synapses. GFP-GLT-1 fusion proteins expressed in astrocytes also formed distinct clusters that lined the edges of astrocyte processes, as well as the tips of filopodia and spine-like structures. Time-lapse 3D confocal imaging in tissue slices revealed that GFP-GLT-1 clusters were dynamically remodeled on a timescale of minutes. Some transporter clusters moved within developing astrocyte branches as filopodia extended and retracted, while others maintained stable positions at the tips of spine-like structures. Blockade of neuronal activity with tetrodotoxin reduced both the density and perisynaptic localization of GLT-1 clusters. Conversely, enhancement of neuronal activity increased the size of GLT-1 clusters and their proximity to synapses. Together, these findings indicate that neuronal activity influences both the organization of glutamate transporters in developing astrocyte membranes and their position relative to synapses.
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影响因子：
5.3
作者：
Haber, Michael;Zhou, Lei;Murai, Keith K.
通讯作者：
Murai, Keith K.
DOI：
10.1016/0165-3806(93)90108-m
发表时间：
1993-01-15
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
BUCHS, PA;STOPPINI, L;MULLER, D
通讯作者：
MULLER, D
DOI：
10.1023/b:neur.0000044189.08240.a2
发表时间：
2004-05-01
期刊：
JOURNAL OF NEUROCYTOLOGY
影响因子：
--
作者：
Hama, K;Arii, T;Ellisman, MH
通讯作者：
Ellisman, MH
影响因子：
2.5
作者：
DESMOND, NL;LEVY, WB
通讯作者：
LEVY, WB
影响因子：
4.8
作者：
Butchbach, MER;Tian, GL;Lin, CLG
通讯作者：
Lin, CLG