A circadian clock in hippocampus is regulated by interaction between oligophrenin-1 and Rev-erbalpha.
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Valnegri P, Khelfaoui M, Dorseuil O, Bassani S, Lagneaux C, Gianfelice A, Benfante R, Chelly J, Billuart P, Sala C, Passafaro M
A circadian clock in hippocampus is regulated by interaction between oligophrenin-1 and Rev-erbalpha.
Nat Neurosci. 2011 Aug 28;14(10):1293-301. doi: 10.1038/nn.2911.
- PubMed ID
- 21874017 [ View in PubMed]
- Abstract
Oligophrenin-1 regulates dendritic spine morphology in the brain. Mutations in the oligophrenin-1 gene (OPHN1) cause intellectual disability. We discovered a previously unknown partner of oligophrenin-1, Rev-erbalpha, a nuclear receptor that represses the transcription of circadian oscillators. We found that oligophrenin-1 interacts with Rev-erbalpha in the mouse brain, causing it to locate to dendrites, reducing its repressor activity and protecting it from degradation. Our results indicate the presence of a circadian oscillator in the hippocampus, involving the clock gene Bmal1 (also known as Arntl), that is modulated by Rev-erbalpha and requires oligophrenin-1 for normal oscillation. We also found that synaptic activity induced Rev-erbalpha localization to dendrites and spines, a process that is mediated by AMPA receptor activation and requires 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.