Transduction of group I mGluR-mediated synaptic plasticity by β-arrestin2 signalling.
Transduction of group I mGluR-mediated synaptic plasticity by β-arrestin2 signalling.
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DOI：
10.1038/ncomms13571
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发表时间：
2016-11-25
影响因子：
16.6
通讯作者：
Swanson, Geoffrey T.
中科院分区：
文献类型：
--
作者：
Eng, Andrew G.;Kelver, Daniel A.;Hedrick, Tristan P.;Swanson, Geoffrey T.
I组代谢型谷氨酸受体mGluR 1和mGluR 5的常规信号传导通过G蛋白偶联发生，但有证据表明它们也可能利用其他非经典效应子途径。在这里，我们测试组I mGluRs是否需要β-arrestin信号在特定形式的可塑性在海马兴奋性突触。我们发现β-arrestin 2的基因切除，而不是β-arrestin 1，导致由mGlu 1受体介导的可塑性在CA 3锥体神经元和mGlu 5受体在CA 1锥体神经元的缺陷。药理学研究还支持Src激酶和β-arrestin 2下游MAPK/ERK在CA 3神经元中的作用。在β-arrestin 2 −/−小鼠中，除了反弹去极化外，mGluR 1对固有电导的调节得以保留，非mGluR介导的长时程增强未发生改变。这些结果揭示了I组mGluRs参与的信号传导途径，以影响依赖于β-抑制蛋白而不是G蛋白的突触和细胞内在生理学的变化。药理学操纵mGluRs与效应偏向配体可能会导致新的疗法来治疗神经系统疾病。 已知mGluRs经历非经典信号传导调节，尽管潜在的机制尚不清楚。在这里，作者确定了β-arrestin 2而不是β-arrestin 1在海马突触I组mGluR介导的可塑性中的作用。
Conventional signalling by the group I metabotropic glutamate receptors, mGluR1 and mGluR5, occurs through G-protein coupling, but evidence suggests they might also utilize other, non-canonical effector pathways. Here we test whether group I mGluRs require β-arrestin signalling during specific forms of plasticity at hippocampal excitatory synapses. We find that genetic ablation of β-arrestin2, but not β-arrestin1, results in deficits in plasticity mediated by mGlu1 receptors in CA3 pyramidal neurons and by mGlu5 receptors in CA1 pyramidal neurons. Pharmacological studies additionally support roles for Src kinases and MAPK/ERK downstream of β-arrestin2 in CA3 neurons. mGluR1 modulation of intrinsic conductances is otherwise preserved in β-arrestin2−/− mice with the exception of a rebound depolarization, and non-mGluR-mediated long-term potentiation is unaltered. These results reveal a signalling pathway engaged by group I mGluRs to effect changes in synaptic and cell intrinsic physiology dependent upon β-arrestin rather than G proteins. Pharmacological manipulation of mGluRs with effector-biased ligands could lead to novel therapies to treat neurological disease. mGluRs are known to undergo non-canonical signalling regulation, although the underlying mechanisms are unclear. Here, the authors identify a role for β-arrestin2, but not β-arrestin1, in group I mGluR-mediated plasticity at hippocampal synapses.
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影响因子：
4.7
作者：
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通讯作者：
Wroblewski JT
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