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

Neuron (2013-04-30)
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
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Actinomycin D, from Streptomyces sp., ~98% (HPLC)
Sigma-Aldrich
Actinomycin D, from Streptomyces sp., suitable for cell culture, ≥95%
Sigma-Aldrich
Actinomycin D, from Streptomyces sp., ≥95% (HPLC)
Sigma-Aldrich
N-Methyl-D-aspartic acid, ≥98% (TLC), solid