Coassembly and Coupling of SK2 Channels and mGlu5 Receptors

Coassembly and Coupling of SK2 Channels and mGlu5 Receptors
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DOI:
10.1523/jneurosci.2038-14.2014
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发表时间:
2014-10-29
影响因子:
5.3
通讯作者:
Ciruela, Francisco
Ciruela, Francisco
中科院分区:
医学1区
文献类型:
--
作者:
Garcia-Negredo, Gloria;Soto, David;Ciruela, Francisco

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I组代谢性谷氨酸(mGlu)受体通过Ca2+波依赖性激活小电导Ca2+激活K+ (SK)通道调节海马CA1锥体神经元的兴奋性。在这里,我们发现mGlu(5)受体和SK2通道在异源共表达系统和大鼠脑中共同聚集。此外,在共转染细胞或大鼠海马原代神经元中,mGlu(5)受体刺激激活了阿帕胺敏感的sk2介导的K+电流。此外,mGlu(5)受体和SK2通道的共表达促进了这两种蛋白的质膜靶向,并与mGlu(5)受体功能的增加相关,而mGlu(5)受体功能意外地被apamin阻断。这些结果表明mGlu(5)受体和SK2通道之间存在互反的功能相互作用,反映了它们的分子共组装。
Group I metabotropic glutamate (mGlu) receptors regulate hippocampal CA1 pyramidal neuron excitability via Ca2+ wave-dependent activation of small-conductance Ca2+-activated K+ (SK) channels. Here, we show that mGlu(5) receptors and SK2 channels coassemble in heterologous coexpression systems and in rat brain. Further, in cotransfected cells or rat primary hippocampal neurons, mGlu(5) receptor stimulation activated apamin-sensitive SK2-mediated K+ currents. In addition, coexpression of mGlu(5) receptors and SK2 channels promoted plasma membrane targeting of both proteins and correlated with increased mGlu(5) receptor function that was unexpectedly blocked by apamin. These results demonstrate a reciprocal functional interaction between mGlu(5) receptors and SK2 channels that reflects their molecular coassembly.