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A circadian clock in hippocampus is regulated by interaction between oligophrenin- 1 and Rev-erbα
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Edité par CCSD ; Nature Publishing Group -
International audience. Oligophrenin-1 regulates dendritic spine morphology in brain. Mutations in the oligophrenin-1 gene cause intellectual disability. We report a new partner of oligophrenin-1, Rev-erbα: a nuclear receptor that represses the transcription of circadian oscillators. We show in mouse brain that oligophrenin-1 interacts with Rev-erbα, causing it to locate to dendrites, reducing its repressor activity, and protecting it from degradation. More importantly we demonstrate a circadian oscillator in hippocampus, involving the clock gene bmal1, modulated by Rev-erbα and requiring oligophrenin-1 for normal oscillation. We also show that synaptic activity induces Rev-erbα localization to dendrites and spines, a process mediated by AMPA receptor activation and requiring oligophrenin-1. Our data reveal new interactions between synaptic activity and circadian oscillators, and delineate a new means of communication between nucleus and synapse that may provide insight into normal plasticity and the etiology of intellectual disability.
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