IIBBA   05544
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE BUENOS AIRES
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Synaptic activity regulates the dynamics of Smaug 1 mRNA-silencing foci
Autor/es:
LUCHELLI L; MASCHI D; PASCUAL M; HABIF M; BAEZ MV; THOMAS MG; BOCCACCIO GL
Lugar:
Viena
Reunión:
Congreso; EMBO; 2012
Institución organizadora:
EMBO
Resumen:
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 that mediate silencing and/or deadenylation. Smaug 1 foci (S-foci) are 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. We found that Smaug 1 aggregation is independent of its repressor activity, and requires a conserved region at the N-terminus. The S-foci are usually static under basal conditions, but highly dynamic upon neuron depolarization or specific stimulation. NMDA or DHPG receptor activation provokes a transient dissolution of the S-foci, allowing mRNA release incorporation into polysomes. The S-foci do not respond to AMPA receptor activation, which provokes the relaxation of the FMRP foci located at dendritic spines, or to the stimulation of GABAergic inhibitory synapses. Using the FUNCAT strategy, we found that DHPG stimulates protein synthesis at the dendrite. In contrast, NMDA suppresses global protein synthesis, and simultaneously stimulates the translation of Smaug 1-repressed messengers. Finally, we found that Smaug 1 knockdown in hippocampal neurons 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