Exploring the F-actin/CPEB3 interaction and its possible role in the molecular mechanism of long-term memory

Significance The growth and stabilization of dendritic spines is thought to be essential for strengthening the connections between neurons and thereby memories. Actin cytoskeleton remodeling in spines is the basis of this growth and stabilization. A functional prion that binds mRNA, CPEB3, which interacts with actin, has been reported to be involved in the maintenance of long-term memory by forming stable aggregates. Here we study the interaction between actin and CPEB3 and propose a molecular model for the complex structure of CPEB3 bound to an actin filament. Our model gives insights into the actin/CPEB3 positive feedback loop underlying long-term memory which involves CPEB3’s binding to actin, its aggregation, and its regulation by SUMOylation.