Region-specific regulation of glucocorticoid receptor/HSP90 expression and interaction in brain
Region-specific regulation of glucocorticoid receptor/HSP90 expression and interaction in brain
复制标题
DOI：
10.1111/j.1471-4159.2006.03953.x
复制
发表时间：
2006-08-01
影响因子：
4.7
通讯作者：
Herman, J. P.
中科院分区：
文献类型：
--
作者：
Furay, A. R.;Murphy, E. K.;Herman, J. P.
海马糖皮质激素受体（GR）参与下丘脑-垂体-肾上腺轴的负反馈调节，并被认为是抑制糖皮质激素在抑郁症和年龄相关性记忆丧失中的有害作用。GR的调节和细胞内运输是健康和疾病中GR作用的关键决定因素。在这里，我们展示了GR的动态调节及其与其主要的细胞内伴侣热休克蛋白（HSP）90的相互作用，在整个昼夜节律周期。我们的初步实验表明，胞浆海马GR蛋白在晚上（PM）升高，而核GR和胞浆HSP 90，HSP 70和热休克同源物70（HSC 70），是不变的。相比之下，下丘脑中检测的蛋白质没有变化。免疫沉淀实验揭示增加GR-HSP 90协会在海马中的PM，而结合在下丘脑中的PM减少。鉴于GR需要HSP 90进行配体结合，数据表明，昼夜GR信号传导能力以区域特异性模式进行调节。
The hippocampal glucocorticoid receptor (GR) is involved in negative feedback regulation of the hypothalamo-pituitary-adrenal axis and is believed to transduce the deleterious effects of glucocorticoids in depression and age-related memory loss. Regulation and intracellular trafficking of the GR are critical determinants of GR action in both health and disease. Here, we show dynamic regulation of GR and its interaction with its principal intracellular chaperone, heat-shock protein (HSP) 90, across the circadian cycle. Our initial experiments indicate that cytosolic hippocampal GR protein is elevated in the evening (PM), whereas nuclear GR and cytosolic HSP90, HSP70 and heat-shock cognate 70 (HSC70), are unchanged. In contrast, there are no changes in examined proteins in the hypothalamus. Immunoprecipitation experiments reveal increased GR-HSP90 associations in the hippocampus in the PM, whereas binding in the hypothalamus is decreased in the PM. Given that GR requires HSP90 for ligand binding, the data suggest that circadian GR signaling capacity is regulated in a region-specific pattern.