Neurite-localized estrogen receptor-α mediates rapid signaling by estrogen
Neurite-localized estrogen receptor-α mediates rapid signaling by estrogen
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DOI：
10.1002/jnr.10725
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发表时间：
2003-10-01
影响因子：
4.2
通讯作者：
Wang, MM
中科院分区：
文献类型：
--
作者：
Xu, Y;Traystman, RJ;Wang, MM
传统意义上，雌激素通过直接激活配体结合核雌激素受体（ER）驱动的基因转录作用于细胞。越来越多的证据表明，雌激素通过多种分子机制作用于神经元，包括定位于质膜的蛋白质的快速信号传导。最近的研究表明，erα定位于海马神经元的轴突和树突，表明受体的非核储存可能转导雌激素信号。在此，我们研究了erα的亚细胞定位、动态调控和功能。小鼠皮质神经元。雌激素刺激小鼠皮质神经元激活雌激素反应元件（ERE）刺激的转录和p44/42丝裂原激活蛋白激酶（MAPK）的快速激活。我们证明了绿色荧光蛋白（GFP）标记的er - alpha定位于培养的皮质神经元的神经突，并且在合成过程中，雌激素可以下调神经突内的表达，抗雌激素可以上调神经突内的表达。神经突erα似乎直接从其翻译位点而不是从核库中被引导到神经突。通过共聚焦显微镜，我们发现神经突内的erα刺激p44/42 MAP激酶的局部激活，以响应雌激素。我们得出的结论是，激素状态改变了皮层神经元的亚细胞erα靶向，神经细胞表达的erα在局部MAPK信号的激活中很重要。(C) 2003 Wiley-Liss, Inc。
Classically, estrogen acts on cells by directly activating gene transcription driven by ligand-bound nuclear estrogen receptors (ER). Accumulating evidence demonstrates that estrogen acts on neurons by utilizing diverse molecular mechanisms, including rapid signaling by proteins localized to the plasma membrane. Recent studies showing that ERalpha localizes to axons and dendrites of hippocampal neurons suggest that nonnuclear stores of the receptor may transduce estrogen signaling. Here, we have studied the subcellular localization, dynamic regulation, and function of ERalpha. in mouse cortical neurons. Estrogen-stimulated mouse cortical neurons activate both estrogen response element (ERE) stimulated transcription and rapid activation of p44/42 mitogen-activated protein kinases (MAPK). We demonstrate that green fluorescent protein (GFP)-tagged ERalpha localizes to neurites in cultured cortical neurons and that the expression within neurites can be down-regulated by estrogen or up-regulated by antiestrogen administered during synthesis. Neurite ERalpha appears to be directed to neurites directly from its site of translation and not from nuclear stores. By using confocal microscopy, we show that ERalpha within neurites stimulates local activation of p44/42 MAP kinases in response to estrogen. We conclude that hormonal status alters subcellular ERalpha targeting in cortical neurons and that neurite-expressed ERalpha is important in the activation of local MAPK signaling. (C) 2003 Wiley-Liss, Inc.