Membrane estrogen receptors activate the metabotropic glutamate receptors mGluR5 and mGluR3 to bidirectionally regulate CREB phosphorylation in female rat striatal neurons.
Membrane estrogen receptors activate the metabotropic glutamate receptors mGluR5 and mGluR3 to bidirectionally regulate CREB phosphorylation in female rat striatal neurons.
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DOI：
10.1016/j.neuroscience.2010.08.012
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发表时间：
2010-11-10
期刊：
影响因子：
3.3
通讯作者：
Mermelstein, P. G.
中科院分区：
文献类型：
--
作者：
Grove-Strawser, D.;Boulware, M. I.;Mermelstein, P. G.
除了直接调节基因表达的能力外，雌二醇还通过快速的膜启动事件影响细胞信号和大脑功能。在雌性大鼠纹状体中，雌二醇激活膜上定位的雌激素受体，影响突触神经传递、钙通道活性和与运动控制相关的行为。然而，雌二醇迅速影响纹状体生理的机制仍然不清楚。在这里，我们发现膜雌激素受体与代谢性谷氨酸受体mGluR5和mGluR3偶联，为理解膜雌激素受体如何影响纹状体功能提供了框架。膜上定位的ERα将CREB磷酸化作为ER/mGluR激活的下游指标，激活mGluR5信号，介导MAPK依赖的CREB磷酸化。此外，ERα和ERβ激活mGluR3可减弱L钙通道依赖的CREB信号。有趣的是，虽然ER/mGluR信号的这一基本机制最初是在海马神经元中表征的，但纹状体神经元中的雌激素受体与一组不同的mGluR配对，导致通过使用特定的mGluR调节剂，在功能上隔离跨脑区域的膜启动的雌激素信号。这些结果既为雌激素在雌性纹状体内的快速作用提供了一种机制，也证明了雌激素受体可以与一组比先前认识的更多样化的表膜受体相互作用。
Along with its ability to directly regulate gene expression, estradiol influences cell signaling and brain functions via rapid, membrane-initiated events. In the female rat striatum, estradiol activates membrane-localized estrogen receptors to influence synaptic neurotransmission, calcium channel activity, and behaviors related to motor control. Yet, the mechanism by which estradiol acts to rapidly affect striatal physiology has remained elusive. Here we find that membrane estrogen receptors couple to the metabotropic glutamate receptors mGluR5 and mGluR3, providing the framework to understand how membrane estrogen receptors affect striatal function. Using CREB phosphorylation as a downstream measure of ER/mGluR activation, membrane-localized ERα activates mGluR5 signaling to mediate MAPK-dependent CREB phosphorylation. Further, ERα and ERβ activate mGluR3 to attenuate L-type calcium channel-dependent CREB signaling. Interestingly, while this fundamental mechanism of ER/mGluR signaling was initially characterized in hippocampal neurons, estrogen receptors in striatal neurons are paired with a different set of mGluRs, resulting in the potential to functionally isolate membrane-initiated estrogen signaling across brain regions, via use of specific mGluR modulators. These results provide both a mechanism for the rapid actions of estrogens within the female striatum, as well as demonstrate that estrogen receptors can interact with a more diverse set of surface membrane receptors than previously recognized.
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影响因子：
7.4
作者：
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影响因子：
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