Disrupted-in-schizophrenia 1 enhances the quality of circadian rhythm by stabilizing BMAL1
| Autor: | Bo Kyoung Suh, Eunbyul Cho, Jihyun Park, Youngsik Woo, Truong Thi My Nhung, Yeongjun Suh, Yongdo Kwak, Sehyung Cho, Young Un Park, Su Been Lee, Sang Ki Park |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Scaffold protein endocrine system Physiology CLOCK Proteins Nerve Tissue Proteins Molecular neuroscience Article lcsh:RC321-571 03 medical and health sciences Cellular and Molecular Neuroscience DISC1 Mice 0302 clinical medicine Ubiquitin Circadian Clocks medicine Animals Circadian rhythm Promoter Regions Genetic Gene lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Biological Psychiatry biology ARNTL Transcription Factors medicine.disease Cell biology Circadian Rhythm Psychiatry and Mental health 030104 developmental biology Schizophrenia Intracellular calcium homeostasis biology.protein 030217 neurology & neurosurgery |
| Zdroj: | Translational Psychiatry, Vol 11, Iss 1, Pp 1-13 (2021) Translational Psychiatry |
| ISSN: | 2158-3188 |
| Popis: | Disrupted-in-schizophrenia 1 (DISC1) is a scaffold protein that has been implicated in multiple mental disorders. DISC1 is known to regulate neuronal proliferation, signaling, and intracellular calcium homeostasis, as well as neurodevelopment. Although DISC1 was linked to sleep-associated behaviors, whether DISC1 functions in the circadian rhythm has not been determined yet. In this work, we revealed that Disc1 expression exhibits daily oscillating pattern and is regulated by binding of circadian locomotor output cycles kaput (CLOCK) and Brain and muscle Arnt-like protein-1 (BMAL1) heterodimer to E-box sequences in its promoter. Interestingly, Disc1 deficiency increases the ubiquitination of BMAL1 and de-stabilizes it, thereby reducing its protein levels. DISC1 inhibits the activity of GSK3β, which promotes BMAL1 ubiquitination, suggesting that DISC1 regulates BMAL1 stability by inhibiting its ubiquitination. Moreover, Disc1-deficient cells and mice show reduced expression of other circadian genes. Finally, Disc1-LI (Disc1 knockout) mice exhibit damped circadian physiology and behaviors. Collectively, these findings demonstrate that the oscillation of DISC1 expression is under the control of CLOCK and BMAL1, and that DISC1 contributes to the core circadian system by regulating BMAL1 stability. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|