Ahi1 regulates the nuclear translocation of glucocorticoid receptor to modulate stress response

Author:

Wang Bin,Xin Ning,Qian Xuanchen,Zhai Lijing,Miao Zhigang,Yang YongORCID,Li ShihuaORCID,Sun MiaoORCID,Xu XingshunORCID,Li Xiao-JiangORCID

Abstract

AbstractStress 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.

Funder

National Natural Science Foundation of China

Publisher

Springer Science and Business Media LLC

Subject

Biological Psychiatry,Cellular and Molecular Neuroscience,Psychiatry and Mental health

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