期刊
NATURE NEUROSCIENCE
卷 14, 期 10, 页码 1293-U108出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nn.2911
关键词
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资金
- Telethon Italy [S01014TELU, GGP09196]
- Fondazione Cariplo [2008-2318, 2009.264]
- Fondazione Mariani
- Project TerDisMental [16983 - Rif.SAL-50]
- Ricerca Scientifica a Tema Libero (RSTL) Consiglio Nazionale delle Ricerche (CNR)
- Regione Lombardia [SAL-50-16983]
- Italian Institute of Technology
- French National Research Agency [ANR-06-Neuro-003-02, ANR-08-MNPS-037-04]
- European Union [241995]
- Fondation Jerome Lejeune
- INSERM
- Fondation pour La Recherche Medicale
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.
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