Regulation of the local translation at the synapse by S-foci

LUCHELLI L; BOCCACCIO GL

Capital Federal

Simposio; Simposio Franco-Argentino de Neurociencias; 2012

Having demonstrating the expression of Smaug 1 in the CNS (Baez and Boccaccio, 2005), we found that Smaug 1 forms granules of approximately 0.5 μm in diameter, which were present in the cell body and dendrites. We named these structures, S-foci, and we observed that these granules behave as mRNA silencing foci and that they are distinct from PBs and independent of them for their maintenance. We found that between 55% of synapses contain S-foci in hippocampal primary cultures and in hippocampal slices between 60% of synapse patches contain 1 or 2 S-foci in their surroundings. We found that Smaug 1 is present in hippocampal synaptosomes. Moreover, Smaug 1 co-purified with PSD95 in post-synaptic densities isolated from synaptosomes. To further assess the role of NMDAR and mGltR in S-foci dynamics, we exposed hippocampal neurons to a short pulse of NMDA and DHPG and we found that the S-foci dissolved upon NMDAR/ mGlutR activation. CamKIIα mRNA is known to be locally translated upon NMDA stimulation and thus, we sought to investigate whether the S-foci are involved in the regulation of this messenger. We found that a proportion of CamKIIα mRNA granules are associated to S-foci. We investigated whether this association is affected by NMDAR stimulation. NMDA exposure provoked the dissolution of the synaptic S-foci and an enhanced of CamKIIα mRNA granules at the synapse. Importantly, the colocalization of S-foci and CamKIIα mRNA granules at the synapses was reduced from 50±3% to 18±3%. We investigated whether S-foci dissolution by NMDA correlates with a global stimulation of local translation. We found that NMDA blocked the incorporation of labeled amino acids wears a pulse with DHPG increase the incorporation of labeled amino acids. All these observations suggest that NMDAR activation locally provokes a global translational silencing, and at the same time allows the translation of CamKIIα mRNA and others unknown mRNAs by triggering S-foci dissolution.