Control of synaptic plasticity and memory via suppression of poly(A)-Binding protein

Arkady Khoutorsky, Akiko Yanagiya, Christos G. Gkogkas, Marc R. Fabian, Masha Prager-Khoutorsky, Ruifeng Cao, Karine Gamache, Frederic Bouthiette, Armen Parsyan, Robert E. Sorge, Jeffrey S. Mogil, Karim Nader, Jean Claude Lacaille, Nahum Sonenberg

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

Control of protein synthesis is critical for synaptic plasticity and memory formation. However, the molecular mechanisms linking neuronal activity to activation of mRNA translation are not fully understood. Here, we report that the translational repressor poly(A)-binding protein (PABP)-interacting protein 2A (PAIP2A), an inhibitor of PABP, is rapidly proteolyzed by calpains in stimulated neurons and following training for contextual memory. Paip2a knockout mice exhibit a lowered threshold for the induction of sustained long-term potentiation and an enhancement of long-term memory after weak training. Translation of CaMKIIα mRNA is enhanced in Paip2a-/- slices upon tetanic stimulation and in the hippocampus of Paip2a-/- mice following contextual fear learning. We demonstrate that activity-dependent degradation of PAIP2A relieves translational inhibition of memory-related genes through PABP reactivation and conclude that PAIP2A is a pivotal translational regulator of synaptic plasticity and memory

Original languageEnglish (US)
Pages (from-to)298-311
Number of pages14
JournalNeuron
Volume78
Issue number2
DOIs
StatePublished - Apr 24 2013

Bibliographical note

Funding Information:
We thank Wayne Sossin and Valerie Henderson for excellent comments; Annie Sylvestre, Sandra Perreault, and Colin Lister for technical assistance; and Isabel Laplante for assistance with immunostaining. This work was supported by National Institutes of Health Grant 2R01GM066157 and a Canadian Institutes of Health Research (CIHR) grant to Nahum Sonenberg and CIHR Grant MOP-10848 to J.C.L. J.C.L. is the recipient of the Canada Research Chair in Cellular and Molecular Neurophysiology.

Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.

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