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Author Notes:

Correspondence: joel.richter@umassmed.edu

Tsuyoshi Udagawa and Sharon A. Swanger contributed equally to this work.

We thank the UMASS Genomics and Bioinformatics Core for help with microarray analysis, Fabrizio Pontarelli for assistance with stereotactic injections, Yuncen A. He for assistance with image analysis, and Kenny Futai for comments on the manuscript.

Subjects:

Research Funding:

TU was supported by a postdoctoral fellowship from the FRAXA Foundation.

SAS was supported by predoctoral fellowships from the NIH F31NS063668, T32GM0860512 and T32NS007480, and the Epilepsy Foundation and Lennox & Lombroso Trust Fund.

This work was supported by NIH grants GM46779, HD37267, and AG30323 (to JDR) and MH085617 (to GJB) and a NARSAD Investigator Award (GJB).

Core support at UMass Medical School from the Diabetes Endocrinology Research Center (P30 DK32520) and the Intellectual and Developmental Disabilities Research Center (P30 HD04147) and at Emory University from the NINDS Microscopy Core (P30NS055077) is acknowledged.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biochemistry & Molecular Biology
  • Cell Biology
  • LONG-TERM POTENTIATION
  • CULTURED HIPPOCAMPAL-NEURONS
  • DENDRITIC PROTEIN-SYNTHESIS
  • MOSSY FIBER SYNAPSES
  • FRAGILE-X-SYNDROME
  • BINDING-PROTEIN
  • DENTATE GYRUS
  • DEPENDENT TRANSLATION
  • CPEB PHOSPHORYLATION
  • GLUTAMATE RECEPTORS

Bidirectional Control of mRNA Translation and Synaptic Plasticity by the Cytoplasmic Polyadenylation Complex

Tools:

Journal Title:

Molecular Cell

Volume:

Volume 47, Number 2

Publisher:

, Pages 253-266

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Translational control of mRNAs in dendrites is essential for certain forms of synaptic plasticity and learning and memory. CPEB is an RNA-binding protein that regulates local translation in dendrites. Here, we identify poly(A) polymerase Gld2, deadenylase PARN, and translation inhibitory factor neuroguidin (Ngd) as components of a dendritic CPEB-associated polyadenylation apparatus. Synaptic stimulation induces phosphorylation of CPEB, PARN expulsion from the ribonucleoprotein complex, and polyadenylation in dendrites. A screen for mRNAs whose polyadenylation is altered by Gld2 depletion identified > 100 transcripts including one encoding NR2A, an NMDA receptor subunit. shRNA depletion studies demonstrate that Gld2 promotes and Ngd inhibits dendritic NR2A expression. Finally, shRNA-mediated depletion of Gld2 in vivo attenuates protein synthesis-dependent long-term potentiation (LTP) at hippocampal dentate gyrus synapses; conversely, Ngd depletion enhances LTP. These results identify a pivotal role for polyadenylation and the opposing effects of Gld2 and Ngd in hippocampal synaptic plasticity.

Copyright information:

© 2012 Elsevier Inc.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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