A GluD Coming-Of-Age Story.

A GluD Coming-Of-Age Story.
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DOI:
10.1016/j.tins.2016.12.004
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发表时间:
2017-03
影响因子:
15.9
通讯作者:
Aricescu AR
Aricescu AR
中科院分区:
医学1区
文献类型:
--
作者:
Yuzaki M;Aricescu AR

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GluD1和GluD2受体构成了gld嗜离子型谷氨酸受体(iGluR)亚家族。由于没有已知的内源性配体,它们一直被称为“孤儿”,在功能上仍然是谜。然而,最近的进展从根本上改变了这种观点。两种GluD受体在比原先认为的更宽的大脑区域表达。对基因敲除小鼠的人类遗传研究和分析显示,它们与多种神经发育和精神疾病有关。内源性配体的发现,加上结构研究,为中枢神经系统突触中GluD信号的机制理解开辟了道路。这些研究还提出了一个假设,即所有iGluRs以及潜在的其他神经递质受体,都依赖于细胞外小分子和蛋白质配体的协同结合来传递生理信号。
The GluD1 and GluD2 receptors form the GluD ionotropic glutamate receptor (iGluR) sub-family. Without known endogenous ligands, they have long been referred to as “orphan” and remained enigmatic functionally. Recent progress has, however, radically changed this view. Both GluD receptors express in wider brain regions than originally thought. Human genetic studies and analyses of knockout mice revealed their involvement in multiple neurodevelopmental and psychiatric disorders. The discovery of endogenous ligands, together with structural investigations, opened the way towards a mechanistic understanding of GluD signaling at central nervous system synapses. These studies have also prompted the hypothesis that all iGluRs, and potentially other neurotransmitter receptors, rely on the cooperative binding of extracellular small-molecule and protein ligands for physiological signaling.
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