Control of Synaptic Plasticity and Memory via Suppression of Poly(A)-Binding Protein

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• 作者：Arkady Khoutorsky¹ ; Akiko Yanagiya¹ ; ⁷ ; Christos G. Gkogkas¹ ; ⁷ ; Marc R. Fabian² ; Masha Prager-Khoutorsky³ ; Ruifeng Cao¹ ; Karine Gamache⁴ ; Frederic Bouthiette⁵ ; Armen Parsyan¹ ; Robert E. Sorge⁶ ; Jeffrey S. Mogil⁶ ; Karim Nader⁴ ; Jean-Claude Lacaille⁵ ; ^{jean-claude.lacaille@umontreal.ca} ; Nahum Sonenberg¹ ; ^{nahum.sonenberg@mcgill.ca}
• 刊名：Neuron
• 出版年：2013
• 出版时间：24 April, 2013
• 年：2013
• 卷：78
• 期：2
• 页码：298-311
• 全文大小：1482 K

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Summary

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 CaMKII¦Á 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.