Institute for Fetology, The First Affiliated Hospital of Soochow University, 215006, Suzhou, China.
Institute of Neuroscience, Soochow University, 215123, Suzhou, China.
Transl Psychiatry. 2021 Mar 29;11(1):188. doi: 10.1038/s41398-021-01305-x.
Stress activates the nuclear translocation of glucocorticoid receptors (GR) to trigger gene expression. Abnormal GR levels can alter the stress responses in animals and therapeutic effects of antidepressants. Here, we reported that stress-mediated nuclear translocation of GR reduced Ahi1 in the stressed cells and mouse brains. Ahi1 interacts with GR to stabilize each other in the cytoplasm. Importantly, Ahi1 deficiency promotes the degradation of GR in the cytoplasm and reduced the nuclear translocation of GR in response to stress. Genetic depletion of Ahi1 in mice caused hyposensitivity to antidepressants under the stress condition. These findings suggest that AHI1 is an important regulator of GR level and may serve as a therapeutic target for stress-related disorders.
应激会激活糖皮质激素受体（GR）的核转位，从而触发基因表达。GR 水平异常会改变动物的应激反应和抗抑郁药的治疗效果。在这里，我们报道了应激介导的 GR 核转位会减少应激细胞和小鼠大脑中的 Ahi1。Ahi1 与 GR 相互作用，在细胞质中稳定彼此。重要的是，Ahi1 缺失会促进 GR 在细胞质中的降解，并减少应激时 GR 的核转位。在小鼠中遗传敲除 Ahi1 会导致抗抑郁药在应激条件下的敏感性降低。这些发现表明，AHI1 是 GR 水平的重要调节剂，可能成为应激相关疾病的治疗靶点。
