A circadian clock in hippocampus is regulated by interaction between oligophrenin-1 and Rev-erb alpha

作者：Valnegri Pamela; Khelfaoui Malik; Dorseuil Olivier; Bassani Silvia; Lagneaux Celine; Gianfelice Antonella; Benfante Roberta; Chelly Jamel; Billuart Pierre; Sala Carlo; Passafaro Maria^*

来源：Nature Neuroscience, 2011, 14(10): 1293-U108.

DOI：10.1038/nn.2911

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-erb alpha, a nuclear receptor that represses the transcription of circadian oscillators. We found that oligophrenin-1 interacts with Rev-erb alpha 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-erb alpha and requires oligophrenin-1 for normal oscillation. We also found that synaptic activity induced Rev-erb alpha 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.

• 出版日期2011-10