Cellular and Molecular Life Sciences

, Volume 71, Issue 12, pp 2219–2239 | Cite as

Synaptic control of local translation: the plot thickens with new characters

  • María Gabriela Thomas
  • Malena Lucía Pascual
  • Darío Maschi
  • Luciana Luchelli
  • Graciela Lidia Boccaccio
Review

Abstract

The production of proteins from mRNAs localized at the synapse ultimately controls the strength of synaptic transmission, thereby affecting behavior and cognitive functions. The regulated transcription, processing, and transport of mRNAs provide dynamic control of the dendritic transcriptome, which includes thousands of messengers encoding multiple cellular functions. Translation is locally modulated by synaptic activity through a complex network of RNA-binding proteins (RBPs) and various types of non-coding RNAs (ncRNAs) including BC-RNAs, microRNAs, piwi-interacting RNAs, and small interference RNAs. The RBPs FMRP and CPEB play a well-established role in synaptic translation, and additional regulatory factors are emerging. The mRNA repressors Smaug, Nanos, and Pumilio define a novel pathway for local translational control that affects dendritic branching and spines in both flies and mammals. Recent findings support a role for processing bodies and related synaptic mRNA-silencing foci (SyAS-foci) in the modulation of synaptic plasticity and memory formation. The SyAS-foci respond to different stimuli with changes in their integrity thus enabling regulated mRNA release followed by translation. CPEB, Pumilio, TDP-43, and FUS/TLS form multimers through low-complexity regions related to prion domains or polyQ expansions. The oligomerization of these repressor RBPs is mechanistically linked to the aggregation of abnormal proteins commonly associated with neurodegeneration. Here, we summarize the current knowledge on how specificity in mRNA translation is achieved through the concerted action of multiple pathways that involve regulatory ncRNAs and RBPs, the modification of translation factors, and mRNA-silencing foci dynamics.

Keywords

mTOR NMDAR ARC/Arg3.1 Abnormal protein aggregation Stress granules EJC 

Notes

Acknowledgments

We are grateful to MV Baez for kindly providing figure panel 3d and to L Benseñor and LJ Martinez Tosar for their critical reading of the manuscript. This work was supported by the following grants: UBACyT X311 from University of Buenos Aires, Argentina, to GLB; PIP 205-2011-2013 from Consejo Nacional de Investigaciones Científicas y Tecnológicas (CONICET) to MGT; and PICT 2010-2339, PICT 2010-1850 and PICT 2011-1301 from Agencia Nacional de Promoción Científica y Tecnológica, (ANPCyT), Argentina, to MGT and GLB.

Supplementary material

18_2013_1506_MOESM1_ESM.tif (6.4 mb)
Supplementary material 1 (TIFF 6598 kb) Caption to suggested cover figure. The mRNA repressor Smaug1/Samd4a affects dendritic spines. Dendritic arbors of Smaug1-knockdown hippocampal neurons (yellow) or of untreated cells (white) show the presence of numerous and thin spines provoked by the loss of Smaug1. Deconvoluted confocal Z-stack images of two ECFP-expressing neurons are overlaid

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Copyright information

© Springer Basel 2013

Authors and Affiliations

  • María Gabriela Thomas
    • 1
    • 2
  • Malena Lucía Pascual
    • 1
    • 2
    • 3
  • Darío Maschi
    • 1
    • 4
  • Luciana Luchelli
    • 1
    • 2
  • Graciela Lidia Boccaccio
    • 1
    • 2
    • 3
  1. 1.Instituto LeloirBuenos AiresArgentina
  2. 2.IIBBA-CONICETBuenos AiresArgentina
  3. 3.Facultad de Ciencias Exactas y NaturalesUniversity of Buenos AiresBuenos AiresArgentina
  4. 4.Department of Cell Biology and PhysiologyWashington University School of MedicineSt. LouisUSA

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