A continuous model of physiological prion aggregation suggests a role for Orb2 in gating long-term synaptic information

The regulation of mRNA translation at the level of the synapse is believed to be fundamental in memory and learning at cellular level. The family of Cytoplasmic Polyadenylation Element Binding (CPEB) proteins emerged as an important RNA binding protein family during development and in adult neurons. Drosophila Orb2 (homolog of mouse CPEB3 protein and of the neural isoform of Aplysia CPEB) has been found to be involved in the translation of plasticity-dependent mRNAs and has been associated to Long Term Memory. Orb2 protein presents two main isoforms, Orb2A and Orb2B, which form an activity induced amyloid-like functional aggregate, that is thought to be the translation-inducing state of the RNA binding protein. Here we present a first two-states continuous differential model for Orb2A-Orb2B aggregation. This model provides new working hypotheses for studying the role of prion-like CPEB proteins in long term synaptic plasticity. Moreover, this model can be used as a first step to integra...

突触层面的mRNA翻译调控，被认为是细胞水平记忆与学习的核心基础。胞质多聚腺苷酸化元件结合蛋白（Cytoplasmic Polyadenylation Element Binding, CPEB）家族已被证实为发育过程及成年神经元中一类关键的RNA结合蛋白家族。果蝇Orb2（为小鼠CPEB3蛋白及海兔CPEB神经亚型的同源物）已被发现参与可塑性相关mRNA的翻译过程，并与长时记忆密切相关。Orb2蛋白存在两种主要亚型：Orb2A与Orb2B，二者可形成活性诱导的淀粉样蛋白样功能性聚集体，该聚集体被认为是该RNA结合蛋白发挥翻译诱导功能的活性状态。本文首次提出了针对Orb2A-Orb2B聚集过程的两态连续微分模型。该模型为研究朊病毒样CPEB蛋白在长时突触可塑性中的作用提供了全新的工作假说。此外，该模型可作为整合……的首个研究步骤。