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

Tsuyoshi Udagawa, Sharon A. Swanger, Koichi Takeuchi, Jong Heon Kim, Vijayalaxmi Nalavadi, Jihae Shin, Lori J. Lorenz, R. Suzanne Zukin, Gary J. Bassell, Joel D. Richter

Research output: Contribution to journalArticle

77 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)253-266
Number of pages14
JournalMolecular Cell
Volume47
Issue number2
DOIs
StatePublished - Jul 27 2012

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Bidirectional Control of mRNA Translation and Synaptic Plasticity by the Cytoplasmic Polyadenylation Complex'. Together they form a unique fingerprint.

  • Cite this

    Udagawa, T., Swanger, S. A., Takeuchi, K., Kim, J. H., Nalavadi, V., Shin, J., Lorenz, L. J., Zukin, R. S., Bassell, G. J., & Richter, J. D. (2012). Bidirectional Control of mRNA Translation and Synaptic Plasticity by the Cytoplasmic Polyadenylation Complex. Molecular Cell, 47(2), 253-266. https://doi.org/10.1016/j.molcel.2012.05.016