Synaptic plasticity, specifically the structural change of dendritic spines is essential for maintaining long-term memory. Actin cytoskeleton remodeling provides the molecular basis for the structural change of synapses. Local synthesis of synaptic proteins, like actin proteins, is required to be triggered on, 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. Experiments have suggested that soluble CPEB3 monomers repress translation, whereas 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, using AWSEM simulation, for how CPEB3 binding to SUMO2, a small ubiquitin-like modifier protein, can regulate the translational control in response to stimulation signal.<br/><br/>More interestingly, cellular experiments have shown that actin cytoskeleton interacts with CPEB3 and facilitates its aggregation, which implies a positive feedback loop between CPEB3 and actin. Here, we have also modeled the complex structure of CPEB3 and actin filament, using AWSEM force field, and further proposed a potential mechanism for the actin-triggered CPEB3 aggregation, to understand the positive feedback loop at molecular level.

Exploring the molecular mechanisms of a prion-like RNA-binding protein, CPEB3, underlying long-term memory

Where thousands of chemistry professionals meet to share ideas and advance scientific and technical knowledge. Spring 2023 abstracts, posters, and presentations will launch at the end of March.

ACS Spring 2023

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.