Mutation of a glutamate receptor motif reveals its role in gating and δ2 receptor channel properties

Mutation of a glutamate receptor motif reveals its role in gating and δ2 receptor channel properties
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DOI:
10.1038/73877
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发表时间:
2000-04-01
影响因子:
25
通讯作者:
Yuzaki, M
Yuzaki, M
中科院分区:
医学1区
文献类型:
--
作者:
Kohda, K;Wang, Y;Yuzaki, M

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尽管它在小脑中很重要,但孤儿谷氨酸受体Delta2的功能尚不清楚。我们在Lurcher小鼠身上检测了一个突变的delta2受体通道,该通道在缺乏配体的情况下是结构性活跃的。因为这个突变是在一个高度保守的基序(YTANLAAF)内,我们测试了它对几个谷氨酸受体的影响。突变的delta2受体表现出明显的通道特性,包括电流-电压关系的双重整流、对多胺拮抗剂的敏感性和中等的钙通透性,而其他结构活性的突变谷氨酸通道在这些方面与野生型通道相似。此外,配体激活电流的动力学也发生了显著改变。我们认为,德尔塔2受体具有与谷氨酸受体类似的功能离子通道孔。该基序可能在谷氨酸受体的通道门控中起作用。
Despite its importance in the cerebellum, the functions of the orphan glutamate receptor delta 2 are unknown. We examined a mutant delta 2 receptor channel in lurcher mice that was constitutively active in the absence of ligand. Because this mutation was within a highly conserved motif (YTANLAAF), we tested its effect on several glutamate receptors. Mutant delta 2 receptors showed distinct channel properties, including double rectification of the current-voltage relationship, sensitivity to a polyamine antagonist and moderate Ca2+ permeability, whereas other constitutively active mutant glutamate channels resembled wildtype channels in these respects. Moreover, the kinetics of ligand-activated currents were strikingly altered. We conclude that the delta 2 receptor has a functional ion channel pore similar to that of glutamate receptors. The motif may have a role in the channel gating of glutamate receptors.