Abstract：
Corticosteroid receptors in the mammalian brain mediate genomic as well as non-genomic actions. Although receptors mediating genomic actions were already cloned 35 years ago, it remains unclear whether the same molecules are responsible for the non-genomic actions or that the latter involve a separate class of receptors. Here we focus on one type of corticosteroid receptors, i.e. the mineralocorticoid receptor (MR). We summarize some of the known properties and the current insight in the localization of the MR in peripheral cells and neurons, especially in relation to non-genomic signaling. Previous studies from our own and other labs provided evidence that MRs mediating non-genomic actions are identical to the ones involved in genomic signaling, but may be translocated to the plasma cell membrane instead of the nucleus. With fixed cell imaging and live cell imaging techniques we tried to visualize these presumed membrane-associated MRs, using antibodies or overexpression of MR-GFP in COS7 and hippocampal cultured neurons. Despite the physiological evidence for MR location in or close to the cell membrane, we could not convincingly visualize membrane localization of endogenous MRs or GFP-MR molecules. However, we did find punctae of labeled antibodies intracellularly, which might indicate transactivating spots of MR near the membrane. We also found some evidence for trafficking of MR via beta-arrestins. In beta-arrestin knockout mice, we didn\'t observe metaplasticity in the basolateral amygdala anymore, indicating that internalization of MRs could play a role during corticosterone activation. Furthermore, we speculate that membrane-associated MRs could act indirectly via activating other membrane located structures like e.g. GPER and/or receptor tyrosine kinases.
摘要：
哺乳动物脑中的皮质类固醇受体介导基因组以及非基因组作用。尽管介导基因组作用的受体在35年前就已经被克隆,目前尚不清楚相同的分子是否负责非基因组作用，或者后者涉及单独的受体类别。这里我们关注一种类型的皮质类固醇受体，即盐皮质激素受体(MR)。我们总结了一些已知的特性和目前对周围细胞和神经元中MR定位的见解，特别是与非基因组信号有关。我们自己和其他实验室的先前研究提供的证据表明，介导非基因组作用的MR与参与基因组信号传导的MR相同，但可能会转移到质膜而不是细胞核。通过固定细胞成像和活细胞成像技术，我们试图可视化这些假定的膜相关MR，在COS7和海马培养的神经元中使用抗体或过表达MR-GFP。尽管有生理证据表明MR位于或靠近细胞膜，我们无法令人信服地可视化内源性MR或GFP-MR分子的膜定位。然而,我们确实在细胞内发现了标记的抗体，这可能表明膜附近的MR转移激活点。我们还发现了一些通过β-抑制素贩运MR的证据。在β-抑制蛋白基因敲除小鼠中,我们不再观察到基底外侧杏仁核的可塑性，表明MR的内在化可能在皮质酮激活过程中发挥作用。此外，我们推测膜相关的MR可以通过激活其他位于膜的结构，例如GPER和/或受体酪氨酸激酶间接发挥作用。
