Gap junctional control of glial glutamate transporter expression
Gap junctional control of glial glutamate transporter expression
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DOI：
10.1016/j.mcn.2007.02.009
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发表时间：
2007-05-01
影响因子：
3.5
通讯作者：
Engele, Juergen
中科院分区：
文献类型：
--
作者：
Figiel, Maciej;Allritz, Claudia;Engele, Juergen
星形胶质细胞摄取谷氨酸是终止谷氨酸能神经传递和防止神经毒性细胞外谷氨酸浓度的主要机制。在这里，我们表明，解偶联培养的皮质星形胶质细胞与差距连接阻断剂，异丙酚，或Cx43模拟肽，Gap 27，抑制GLT-1的表达，主要的谷氨酸转运蛋白亚型在皮质。GLT-1表达对间隙连接的依赖性通过使用星形胶质细胞得到进一步证实，在星形胶质细胞中，主要的星形胶质细胞间隙连接蛋白Cx43的表达被RNA干扰抑制，或者来自携带Cx43基因的星形胶质细胞特异性缺失的动物。在这两种情况下，减少星形胶质细胞耦合与GLT-1表达的显着下降。最后，荧光素酶报告基因分析表明，间隙连接/连接蛋白的阻断抑制GLT-1启动子的转录活性。这些观察结果揭示了以前未被认识的作用，间隙连接在控制神经胶质细胞谷氨酸转运。(C)2007爱思唯尔公司All rights reserved.
The uptake of glutamate into astroglia is the predominant mechanism to terminate glutamatergic neurotransmission and to prevent neurotoxic extracellular glutamate concentrations. Here, we show that uncoupling cultured cortical astrocytes with the gap junction blocker, propofol, or the Cx43 mimetic peptide, Gap27, inhibits the expression of GLT-1, the major glutamate transporter subtype in the cortex. The dependence of GLT-1 expression on gap junctions was further confirmed by the use of astrocytes in which either the expression of Cx43, the major astrocytic gap junction protein, was inhibited by RNA interference or which were derived from animals carrying an astrocyte-specific deletion of the Cx43 gene. In both cases, reduced astrocytic coupling was associated with a pronounced decline in GLT-1 expression. Finally, a luciferase reporter gene assay demonstrated that blockade of gap junctions/connexins suppressed transcriptional activity of GLT-1 promoter. These observations unravel a previously unrecognized role of gap junctions in the control of glial glutamate transport. (C) 2007 Elsevier Inc. All rights reserved.