The role of putative prion-like protein, CPEB2, in translation and long-term memory

Abstract

CPEB proteins are a family of four mRNA-binding protein paralogs that regulate the synthesis of proteins required for a number of important cellular process. CPEB proteins act by binding to the CPE elements present on the 3’UTR of target mRNAs. One process regulated by CPEB is synaptic plasticity and long-term memory. A feature of the some CPEB members is their sequence similarity to a unique class of proteins, known as prion-like proteins that use distinct conformation states to regulate their function. It has been hypothesized that mammalian CPEB proteins employ a similar mechanism to induce the stable changes in synaptic activity required for memory maintenance. Previous studies implicated the CPEB family member, CPEB2, in synaptic plasticity and long-term memory. However, the function of the CPEB2 prion-like sequence is still unknown and this thesis evaluates the function of CPEB2 prion-like sequence in translation regulation and memory. The initial experiments demonstrate CPEB2 forms SDS-resistant oligomers in neurons. We generated an isoform specific CPEB2 knockout mouse that removed exon 1 and the prion-like sequence. We tested the ability of this knockout mice to form oligomeric structures, regulate translation, and form long-lasting memory. The results show that the CPEB2 isoform containing the prion-like sequence regulates expression of key memory molecules, and is required for synaptic plasticity and memory.