title: Control of synaptic plasticity and memory via suppression of poly(A)-binding protein.
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.
authors.affiliation: Department of Biochemistry and Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montréal, QC H3A 1A3, Canada.
authors.forename: Arkady
authors.initials: A
authors.lastname: Khoutorsky
authors.forename: Akiko
authors.initials: A
authors.lastname: Yanagiya
authors.forename: Christos G
authors.initials: CG
authors.lastname: Gkogkas
authors.forename: Marc R
authors.initials: MR
authors.lastname: Fabian
authors.forename: Masha
authors.initials: M
authors.lastname: Prager-Khoutorsky
authors.forename: Ruifeng
authors.initials: R
authors.lastname: Cao
authors.forename: Karine
authors.initials: K
authors.lastname: Gamache
authors.forename: Frederic
authors.initials: F
authors.lastname: Bouthiette
authors.forename: Armen
authors.initials: A
authors.lastname: Parsyan
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sorge
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Mogil
authors.forename: Karim
authors.initials: K
authors.lastname: Nader
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lacaille
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
mesh_terms: D000251:Adenosine Triphosphatases / Q000494:pharmacology; D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002154:Calpain / Q000494:pharmacology; D002478:Cells, Cultured; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D003609:Dactinomycin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005239:Fear / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D039102:Poly(A)-Binding Proteins; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D012097:Repressor Proteins; D013569:Synapses / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D009838:Oligodeoxyribonucleotides; C569621:Paip2 protein, mouse; D039102:Poly(A)-Binding Proteins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; C027903:oligo (dT); D003609:Dactinomycin; D016202:N-Methylaspartate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002154:Calpain; D000251:Adenosine Triphosphatases; C029321:calcium potassium ATPase