PMID- 23365227
OWN - NLM
STAT- MEDLINE
DCOM- 20130402
LR  - 20211021
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 33
IP  - 5
DP  - 2013 Jan 30
TI  - Selective regulation of GluA subunit synthesis and AMPA receptor-mediated 
      synaptic function and plasticity by the translation repressor 4E-BP2 in 
      hippocampal pyramidal cells.
PG  - 1872-86
LID - 10.1523/JNEUROSCI.3264-12.2013 [doi]
AB  - The eukaryotic initiation factor 4E-binding protein-2 (4E-BP2) is a repressor of 
      cap-dependent mRNA translation and a major downstream effector of the mammalian 
      target of rapamycin (mTOR) implicated in hippocampal long-term synaptic 
      plasticity and memory. Yet, synaptic mechanisms regulated by 4E-BP2 translational 
      repression remain unknown. Combining knock-out mice, whole-cell recordings, spine 
      analysis, and translation profiling, we found that 4E-BP2 deletion selectively 
      upregulated synthesis of glutamate receptor subunits GluA1 and GluA2, 
      facilitating AMPA receptor (AMPAR)-mediated synaptic transmission and affecting 
      translation-dependent chemically induced late long-term potentiation (cL-LTP). In 
      4E-BP2 knock-out (4E-BP2(-/-)) mice, evoked and miniature EPSCs were increased, 
      an effect mimicked by short-hairpin RNA knockdown of 4E-BP2 in wild-type mice, 
      indicating that 4E-BP2 level regulates basal transmission at mature hippocampal 
      AMPAR-containing synapses. Remarkably, in 4E-BP2(-/-) mice, the AMPA to NMDA 
      receptor (NMDAR) EPSC ratio was increased, without affecting NMDAR-mediated 
      EPSCs. The enhanced AMPAR function concurred with increased spine density and 
      decreased length resulting from greater proportion of regular spines and less 
      filopodia in 4E-BP2(-/-) mice. Polysome profiling revealed that translation of 
      GluA1 and GluA2 subunits, but not GluN1 or GluN2A/B, was selectively increased in 
      4E-BP2(-/-) hippocampi, consistent with unaltered I-V relation of EPSCs mediated 
      by GluA1/GluA2 heteromers. Finally, translation-dependent cL-LTP of unitary EPSCs 
      was also affected in 4E-BP2(-/-) mice, lowering induction threshold and removing 
      mTOR signaling requirement while impairing induction by normal stimulation. Thus, 
      translational control through 4E-BP2 represents a unique mechanism for selective 
      regulation of AMPAR synthesis, synaptic function, and long-term plasticity, 
      important for hippocampal-dependent memory processes.
FAU - Ran, Israeli
AU  - Ran I
AD  - Groupe de Recherche sur le Systeme Nerveux Central and Departement de 
      Physiologie, Universite de Montreal, Montreal, Quebec H3C 3J7, Canada.
FAU - Gkogkas, Christos G
AU  - Gkogkas CG
FAU - Vasuta, Cristina
AU  - Vasuta C
FAU - Tartas, Maylis
AU  - Tartas M
FAU - Khoutorsky, Arkady
AU  - Khoutorsky A
FAU - Laplante, Isabel
AU  - Laplante I
FAU - Parsyan, Armen
AU  - Parsyan A
FAU - Nevarko, Tatiana
AU  - Nevarko T
FAU - Sonenberg, Nahum
AU  - Sonenberg N
FAU - Lacaille, Jean-Claude
AU  - Lacaille JC
LA  - eng
GR  - MOP-10848/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Eif4ebp2 protein, mouse)
RN  - 0 (Eukaryotic Initiation Factors)
RN  - 0 (Protein Subunits)
RN  - 0 (Receptors, AMPA)
SB  - IM
MH  - Animals
MH  - Cerebral Cortex/cytology/metabolism
MH  - Dendritic Spines/metabolism
MH  - Eukaryotic Initiation Factors/genetics/*metabolism
MH  - Excitatory Postsynaptic Potentials/physiology
MH  - Hippocampus/cytology/*metabolism
MH  - Inhibitory Postsynaptic Potentials/physiology
MH  - Long-Term Potentiation/*physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Miniature Postsynaptic Potentials/physiology
MH  - Patch-Clamp Techniques
MH  - Protein Biosynthesis
MH  - Protein Subunits/genetics/*metabolism
MH  - Pyramidal Cells/cytology/*metabolism
MH  - Receptors, AMPA/genetics/*metabolism
MH  - Synapses/*metabolism
MH  - Synaptic Transmission/physiology
PMC - PMC6619136
EDAT- 2013/02/01 06:00
MHDA- 2013/04/03 06:00
PMCR- 2013/07/30
CRDT- 2013/02/01 06:00
PHST- 2013/02/01 06:00 [entrez]
PHST- 2013/02/01 06:00 [pubmed]
PHST- 2013/04/03 06:00 [medline]
PHST- 2013/07/30 00:00 [pmc-release]
AID - 33/5/1872 [pii]
AID - 3818565 [pii]
AID - 10.1523/JNEUROSCI.3264-12.2013 [doi]
PST - ppublish
SO  - J Neurosci. 2013 Jan 30;33(5):1872-86. doi: 10.1523/JNEUROSCI.3264-12.2013.