Caveolin proteins are essential for distinct effects of membrane estrogen receptors in neurons
Caveolin proteins are essential for distinct effects of membrane estrogen receptors in neurons
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DOI：
10.1523/jneurosci.1647-07.2007
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发表时间：
2007-09-12
影响因子：
5.3
通讯作者：
Mermelstein, Paul G.
中科院分区：
文献类型：
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作者：
Boulware, Marissa I.;Kordasiewicz, Holly;Mermelstein, Paul G.
雌二醇除了能够直接调节基因表达外，还通过快速的膜启动事件影响细胞信号传导和脑功能，这一点已被广泛接受。许多这些新的信号传导过程依赖于定位于神经元膜的雌激素受体（er）。然而，内质网在靶向神经元膜表面时能够触发细胞信号传导的机制尚未确定。在海马神经元中，我们发现雌二醇激活代谢性谷氨酸受体（mGluR）信号后，小窝蛋白对CREB （cAMP反应元件结合蛋白）磷酸化的调控至关重要。此外，小窝蛋白-1 （CAV1）和CAV3调节雌二醇激活两个独立信号通路的能力存在差异。mGluR1a的ER α激活依赖于CAV1，而CAV3对于mGluR2/3的ER α和ER β激活是必需的。这些结果与之前在非神经元细胞中的报道一致，暗示了小窝蛋白在快速雌激素信号传导中的重要性。此外，不同的小窝蛋白对不同的雌激素敏感信号通路的功能分离表明，雌二醇的膜启动效应是通过新的机制来协调的。
It has become widely accepted that along with its ability to directly regulate gene expression, estradiol also influences cell signaling and brain function via rapid membrane-initiated events. Many of these novel signaling processes are dependent on estrogen receptors (ERs) localized to the neuronal membrane. However, the mechanism(s) by which ERs are able to trigger cell signaling when targeted to the neuronal membrane surface has yet to be determined. In hippocampal neurons, we find that caveolin proteins are essential for the regulation of CREB (cAMP response element-binding protein) phosphorylation after estradiol activation of metabotropic glutamate receptor (mGluR) signaling. Furthermore, caveolin-1 (CAV1) and CAV3 differentially regulate the ability of estradiol to activate two discrete signaling pathways. ER alpha activation of mGluR1a is dependent on CAV1, whereas CAV3 is necessary for ER alpha and ER beta activation of mGluR2/3. These results are consistent with previous reports in non-neuronal cells, implicating the importance of caveolin proteins in rapid estrogen signaling. In addition, the functional isolation of distinct estrogen-sensitive signaling pathways by different caveolin proteins suggests novel mechanisms through which the membrane-initiated effects of estradiol are orchestrated.