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

• Type of Material: Article
• Authors: Tsuyoshi Udagawa, University of Massachusetts; Sharon Swanger, Emory University; Koichi Takeuchi, Albert Einstein College of Medicine; Jong Heon Kim, University of Massachusetts; Vijayalaxmi Nalavadi, Emory University; Jihae Shin, University of Massachusetts; Lori J. Lorenz, University of Massachusetts; R. Suzanne Zukin, Albert Einstein College of Medicine; Gary Bassell, Emory University; Joel D. Richter, University of Massachusetts
• Language: English
• Date: 2012-07-27
• Publisher: Elsevier (Cell Press): 12 month embargo
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.molcel.2012.05.016
• Title of Journal or Parent Work: Molecular Cell
• ISSN: 1097-2765
• Volume: 47
• Issue: 2
• Start Page: 253
• End Page: 266
• Grant/Funding Information: 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.; SAS was supported by predoctoral fellowships from the NIH F31NS063668, T32GM0860512 and T32NS007480, and the Epilepsy Foundation and Lennox & Lombroso Trust Fund.; TU was supported by a postdoctoral fellowship from the FRAXA Foundation.
• Keywords: GLUTAMATE RECEPTORS; Cell Biology; DENTATE GYRUS; BINDING-PROTEIN; Science & Technology; FRAGILE-X-SYNDROME; CULTURED HIPPOCAMPAL-NEURONS; Life Sciences & Biomedicine; DENDRITIC PROTEIN-SYNTHESIS; MOSSY FIBER SYNAPSES; CPEB PHOSPHORYLATION; Biochemistry & Molecular Biology; LONG-TERM POTENTIATION; DEPENDENT TRANSLATION
• Research Categories: Biology, Cell; Biology, Neuroscience

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.