SHORT TALK: Synaptic activity regulates the dynamics of Smaug 1 mRNA-silencing foci

LUCHELLI, LUCIANA; MASCHI, D; PASCUAL, MALENA; HABIF, MARTIN; BAEZ, M VERÓNICA; THOMAS, M.GABRIELA; BOCCACCIO, GRACIELA L

Congreso; 9th International Conference on Intracellular RNA Localization and Localized Translation; 2011

EMBO

Processing bodies (PBs) and distinct RNA granules govern mRNA transport and local translation in neurons. Here we describe a novel kind of RNA granules, which are restricted to mature neurons, and associated to synapses. These foci contain Smaug 1, a member of a novel family of mRNA regulators. Smaug 1 foci (S-foci) are clearly distinct from PBs, stress granules, or any other previously described neuronal RNA granule, including Fragile X Mental Retardation Protein (FMRP) granules. S-foci behave as mRNA silencing foci, as they are in dynamic equilibrium with translating polysomes. Smaug 1 aggregation is independent of its mRNA repressor activity, and requires a conserved region at the N-terminus. S-foci are in contact with PBs, which appear to be induced as a consequence of Smaug 1-mediated translation repression. To test the hypothesis that Smaug 1-mediated silencing is locally regulated by synaptic activity, we stimulated cultured neurons, and found that S-foci are usually static under basal conditions, and highly dynamic upon specific neuron stimulation. S-foci do not respond to GABA nor to AMPA receptor activation, which provokes the relaxation of the FMRP to foci located at dendritic spines. In contrast, NMDA receptor activation provokes a transient dissolution of the S-foci, allowing the release of mRNAs and their incorporation into polysomes. While NMDA suppresses the Smaug 1-dependent translational silencing, it represses global protein synthesis, as visualized by the FUNCAT strategy. Accordingly, NMDAR activation enhances the presence of a subset of PBs located in dendritic spines. In contrast, DHPG induces the dissolution of both, S-foci and PBs, and stimulates global protein synthesis. Finally, we found that Smaug 1 knockdown affects synaptogenesis, provokes the presence of immature synapses, and impairs the response to synaptic stimulation. Collectively, these observations highlight the selective use of distinct mRNA silencing foci for the fine tuning of local protein synthesis at the synapse, and suggest an important role for the Smaug 1 translation repression pathway on mammalian synaptogenesis.