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

BAEZ MV; LUCHELLI L (1°AUTORIA COMPARTIDA); MASCHI D; HABIF M; PASCUAL M; THOMAS MG; BOCCACCIOB GL

JOURNAL OF CELL BIOLOGY

ROCKEFELLER UNIV PRESS

Lugar: New York; Año: 2011 vol. 195 p. 1141 - 1157

0021-9525

Mammalian Smaug1/Samd4A is a translationalrepressor. Here we show that Smaug1 formsmRNA-silencing foci located at postsynapsesof hippocampal neurons. These structures, which we havenamed S-foci, are distinct from P-bodies, stress granules,or other neuronal RNA granules hitherto described,and are the first described mRNA-silencing foci specificto neurons. RNA binding was not required for aggregation,which indicates that S-foci formation is not aconsequence of mRNA silencing. N-methyl-d-asparticacid (NMDA) receptor stimulation provoked a rapid andreversible disassembly of S-foci, transiently releasingtranscripts (the CaMKII mRNA among others) to allowtheir translation. Simultaneously, NMDA triggered globaltranslational silencing, which suggests the specific activationof Smaug1-repressed transcripts. Smaug1 is expressed duringsynaptogenesis, and Smaug1 knockdown affectedthe number and size of synapses, and also provoked animpaired response to repetitive depolarizing stimuli, asindicated by a reduced induction of Arc/Arg3.1. Ourresults suggest that S-foci control local translation, specificallyresponding to NMDA receptor stimulation andaffecting synaptic plasticity.