The Molecular Mechanisms underlying the Translational Control by a Prion-like RNA-binding Protein, CPEB3, in dendritic spines*

Synaptic plasticity, specifically the structural change of dendritic spines is essential for maintaining long-term memory. Local synthesis of synaptic proteins provides the molecular basis for the structural change of synapses, in response to input signals. CPEB3, a functional prion that binds RNA, has been proposed as a synaptic tag to regulate local translation of target mRNAs in spines. Cellular experiments have shown that soluble CPEB3 monomers repress translation, whereas in contrast CPEB3 aggregates activate the translation of its target mRNAs. However, how this bi-directional translational control is realized and regulated remains unclear. We proposed a mathematical model to show that the vectorial nature of translation, coupled with the polarized structure of mRNA/CPEB3 assemblies determines the direction and significance of the translational control. We also built a structural dynamics model for how CPEB3 binding to SUMO2, a small ubiquitin-like modifier protein, can regulate the translational control in response to stimulation signal.