期刊
JOURNAL OF NEUROSCIENCE RESEARCH
卷 87, 期 1, 页码 12-25出版社
WILEY
DOI: 10.1002/jnr.21824
关键词
dendritic mRNA; activity-dependent translation; RNA-binding protein; plasticity
资金
- INSERM
- Universite Joseph Fourier
- Ministere de l'Enseignement Superieur et de la Recherche
- Association pour la Recherche contre le Cancer (ARC)
- Fondation pour la Recherche Medicale
In cultured hippocampal neurons and in adult brain, the splicing regulatory protein Sam68 is partially relocated to the somatodendritic domain and associates with dendritic polysomes. Transfer to the dendrites is activity-dependent. We have investigated the repertoire of neuronal mRNAs to which Sam68 binds in vivo. By using coimmunoprecipitation and microarray screening techniques, Sam68 was found to associate with a number of plasticity-related mRNA species, including Eef1a1, an activity-responsive mRNA coding for translation elongation factor eEF1A. In cortical neuronal cultures, translation of the Eef1a1 mRNA was strongly induced by neuronal depolarisation and correlated with enhanced association of Sam68 with polysomal mRNAs. The possible function of Sam68 in Eef1a1 mRNA utilization was studied by expressing a dominant-negative, cytoplasmic Sam68 mutant (GFP-Sam68 Delta C) in cultured hippocampal neurons. The level of eEF1A was lower in neurons expressing GFP-Sam68 Delta C than in control neurons, supporting the proposal that endogenous Sam68 may contribute to the translational efficiency of the Eef1a1 mRNA. These findings are discussed in the light of the complex, potentially crucial regulation of eEF1A biosynthesis during long-term synaptic change. (C) 2008 Wiley-Liss, Inc.
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