Smaug1 mRNA-silencing foci respond to NMDA and modulate synapse formation

Abstract

Mammalian Smaug1/Samd4A is a translational repressor. Here we show that Smaug1 forms mRNA-silencing foci located at postsynapses of hippocampal neurons. These structures, which we have named S-foci, are distinct from P-bodies, stress granules, or other neuronal RNA granules hitherto described, and are the first described mRNA-silencing foci specific to neurons. RNA binding was not required for aggregation, which indicates that S-foci formation is not a consequence of mRNA silencing. N-methyl-D-aspartic acid (NMDA) receptor stimulation provoked a rapid and reversible disassembly of S-foci, transiently releasing transcripts (the CaMKIIα mRNA among others) to allow their translation. Simultaneously, NMDA triggered global translational silencing, which suggests the specific activation of Smaug1-repressed transcripts. Smaug1 is expressed during synaptogenesis, and Smaug1 knockdown affected the number and size of synapses, and also provoked an impaired response to repetitive depolarizing stimuli, as indicated by a reduced induction of Arc/Arg3.1. Our results suggest that S-foci control local translation, specifically responding to NMDA receptor stimulation and affecting synaptic plasticity. © 2011 Baez et al.