A novel action of stargazin as an enhancer of AMPA receptor activity
A novel action of stargazin as an enhancer of AMPA receptor activity
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DOI：
10.1016/j.neures.2004.10.002
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发表时间：
2004-12-01
影响因子：
2.9
通讯作者：
Sakimura, K
中科院分区：
文献类型：
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作者：
Yamazaki, M;Ohno-Shosaku, T;Sakimura, K
Stargazin（gamma-2）在共济失调和癫痫突变小鼠stargazer（stg）中被破坏。stg小脑的显著缺陷是颗粒细胞上缺乏功能性AMPA受体。近年来研究发现，γ-2及其相关分子对AMPA受体的表面表达、突触靶向和再循环至关重要，统称为跨膜AMPA受体调节蛋白（TARP）。然而，目前还不清楚TARP是否直接调节AMPA受体活性。在这里，我们报告，共表达GluRalpha 1（GluR 1）与γ-2使用HEK 293细胞和爪蟾卵母细胞显着增强谷氨酸诱导的电流。这种作用远远超过AMPA受体表面表达的增加，并伴随着谷氨酸亲和力和亚基协同性的增加。TARP的其他成员（gamma-3、gamma-4和gamma-8）也通过AMPA受体增强电流响应。γ-2共表达的增强效应进一步观察到同源GluR 2通道，当单独表达时，已知其仅产生小的或可忽略的电流响应。这些结果表明，γ-2不仅促进AMPA受体表面表达，而且直接调节AMPA受体活性。(C)2004年Elsevier爱尔兰有限公司和日本神经科学学会。All rights reserved.
Stargazin (gamma-2) is disrupted in the ataxic and epileptic mutant mouse, stargazer (stg). The striking defect in the stg cerebellum is the lack of functional AMPA receptors on granule cells. Recently, it has been reported that gamma-2 and its related molecules are crucial for the surface expression, synaptic targeting and recycling of AMPA receptors, being termed collectively as the transmembrane AMPA receptor regulatory proteins (TARPs). However, it is still unclear whether TARPs directly modulate AMPA receptor activity. Here we report that coexpression of GluRalpha1 (GluR1) with gamma-2 using HEK293 cells and Xenopus oocytes markedly enhanced glutamate-induced currents. This effect was far beyond the increase of AMPA receptor surface expression and accompanied by increased glutamate affinity and subunit cooperativity. Other member of TARPs (gamma-3, gamma-4, and gamma-8) also enhanced the current response through the AMPA receptors. The enhancing effect by gamma-2 coexpression was further observed for homomeric GluRalpha2 (GluR2) channels, which, when expressed alone, are known to produce only a small or negligible current response. These results suggest that gamma-2 not only promotes AMPA receptor surface expression but also directly modulates AMPA receptor activity. (C) 2004 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.