Fig. 1

A hCPEB3 is present in multiple cellular compartments. Dendritic stimulation leads to temporary, phosphorylation-mediated short-term memory and increased synthesis of the protein CPEB3 (1). Composed of an N-terminal disordered region (black) which includes a Q-rich segment aiding functional aggregation (magenta), hCPEB3 also contains RRM domains (cyan) and a ZZ-Zinc finger domain (turquoise). Upon continued neuro-stimulation, CPEB3 enters the nucleus through the nuclear pore (light magenta), which is a macromolecular condensate (2). Once in the nucleus, CPEB3 indirectly regulates transcription through STAT5B (3) and binds to certain mRNAs (4, red). This binding suppresses translation. After exiting the nucleus through the nuclear pore, (5) CPEB3 + mRNA may associate with a stress granule (6, rose) during moments of adverse conditions. In the absence of stress (7) or its passing (8), CPEB3 + mRNA will combine with another condensate called neuronal granules (light green) for transport to dendritic spines (9), where CPEB3 + mRNA associate with still another class of condensate called a dendritic P-body-like structure (golden) [21]. Further neuronal stimulation (10) causes synapse-specific deSUMOlyation, CPEB3 aggregation, and translational activation of previously repressed mRNA, leading to morphological changes and fortification of the spine, which is proposed to be the basis of long-term memory. This is a simplified model based on that of Kandel and coworkers [22]. B CPEB3 domain composition and its N-terminal intrinsically disordered domain (gray) contains key elements with preferred conformers colored blue for α-helix, magenta for polar amyloidogenic, black for hydrophobic amyloidogenic, green for PPII helix, purple for the putative phosphoTyr site, and red for highly disordered segments. The two RRM domain are colored cyan and the C-terminal Zinc Finger is shown in turquoise