Smaug1 mRNA-silencing foci respond to NMDA and modulate synapse formation.
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.
Fundación Instituto Leloir, C1405BWE Buenos Aires, Argentina.
María Verónica
MV
Baez
Luciana
L
Luchelli
Darío
D
Maschi
Martín
M
Habif
Malena
M
Pascual
María Gabriela
MG
Thomas
Graciela Lidia
GL
Boccaccio
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism; D020868:Gene Silencing / Q000187:drug effects*; D006367:HeLa Cells; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011132:Polyribosomes / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists / Q000378:metabolism; D012097:Repressor Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism*
D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D012097:Repressor Proteins; C507993:SAMD4A protein, human; D016202:N-Methylaspartate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2