Smaug1 mRNA -silencing foci respond to NMDA and modulates synapse formation (SELECTED BY FACULTY OF 1000)

BAEZ, MV; LUCHELLI L; MASCHI, D; HABIF, MARTIN; MALENA PASCUAL,; M. G. THOMAS,; BOCCACCIO GL

JOURNAL OF CELL BIOLOGY

ROCKEFELLER UNIV PRESS

Año: 2011 vol. 195 p. 1141 - 1157

0021-9525

Mammalian Smaug1/Samd4A is a translational repressor. Here we show that Smaug1 forms mRNA-silencing foci located at post-synapses of hippocampal neurons. These structures, which we have named S-foci, are distinct from P-bodies, stress granules or other neuronal RNA granule hitherto described, and are the first reported mRNA-silencing foci specific to neurons. RNA binding was not required for aggregation, indicating that S-foci formation is not a consequence of mRNA silencing. NMDA receptor stimulation provoked a rapid and reversible disassembly of S-foci, transiently releasing transcripts -the CamKIIá mRNA among others- to allow their translation. Simultaneously, NMDA triggered global translational silencing, suggesting the specific activation of Smaug1-repressed transcripts. Smaug1 is expressed during synaptogenesis, and Smaug1 knockdown affected the number and size of synapses and 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 NMDAR stimulation, and affecting synaptic plasticity.