Effects of coexpression with Homer isoforms on the function of metabotropic glutamate receptor 1α
Effects of coexpression with Homer isoforms on the function of metabotropic glutamate receptor 1α
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DOI：
10.1016/s1044-7431(03)00052-6
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发表时间：
2003-06-01
影响因子：
3.5
通讯作者：
Kubo, Y
中科院分区：
文献类型：
--
作者：
Abe, H;Misaka, T;Kubo, Y
我们之前表明，代谢型谷氨酸受体 1α (mGluR1α) 对细胞外多价阳离子（例如 Ca2+ 和 Gd3+）以及谷氨酸具有敏感性。在这里，我们表明 mGluR1alpha 介导的对这些配体的反应是由支架蛋白 Homer 调节的。当 HEK293 细胞瞬时共转染 Homer 1c 和 mGluR1alpha 时，谷氨酸诱发的 [Ca2+](i) 瞬变的最大上升速率和幅度增加，并且浓度-反应关系出现右移。 mGluR1alpha 对 [Gd3+] 突然增加的反应。其特点是浓度-反应关系呈钟形，Homer 1c 在低浓度和高浓度下均拓宽了有效范围。缺乏聚类效应的 Homer I a 的效果与 Homer 1c 的效果有质的不同。在缺乏与 Homer 亲和力的 mGluR1α P1147E 突变体中，Homer 1c 和 1a 对 mGluR1α 的影响均显着降低，表明该影响是通过与 mGluR1α 结合介导的。综上所述，Homer 1c 与 mGluR1alpha 的结合不仅导致与 Ca2+ 存储的有效连接和表面表达的减少，而且还以配体类型特异性的方式引起配体感应功能的质变。 (C) 2003 年爱思唯尔科学（美国）。版权所有。
We previously showed that the metabotropic glutamate receptor 1alpha (mGluR1alpha) has a sensitivity to extracellular polyvalent cations such as Ca2+ and Gd3+ as well as glutamate. Here we show that mGluR1alpha-mediated responses to these ligands are modulated by the scaffold protein Homer. When HEK293 cells were transiently cotransfected with Homer 1c and mGluR1alpha, the maximum rate of rise and amplitude of glutamate-evoked [Ca2+](i) transients were increased and there was a rightward shift in the concentration-response relationship. The response of mGluR1alpha to abrupt increases in [Gd3+]. was characteristic in that the concentration-response relationship was bell-shaped and Homer 1c broadened the effective range at both low and high concentrations. The effects of Homer I a, which lacks clustering effect, differed qualitatively from those of Homer 1c. The effects of both Homer 1c and 1a on mGluR1alpha were decreased significantly in mGluR1alpha P1147E mutant which lacks the affinity to Homer, showing that the effects were mediated by binding to mGluR1alpha. Taken together, the binding of Homer 1c to mGluR1alpha was shown to cause not only an efficient link to Ca2+-store and a decrease in the surface expression, but also qualitative changes of the ligand-sensing function in a ligand type-specific manner. (C) 2003 Elsevier Science (USA). All rights reserved.