Role of CPEB3 protein in learning and memory: new insights from synaptic plasticity

The cytoplasmic polyadenylation element-binding (CPEB) protein family have demonstrated a crucial role for establishing synaptic plasticity and memory in model organisms. In this review, we outline evidence for CPEB3 as a crucial regulator of learning and memory, citing evidence from behavioral, electrophysiological and morphological studies. Subsequently, the regulatory role of CPEB3 is addressed in the context of the plasticity-related proteins, including AMPA and NMDA receptor subunits, actin, and the synaptic scaffolding protein PSD95. Finally, we delve into some of the more well-studied molecular mechanisms that guide the functionality of this dynamic regulator both during synaptic stimulation and in its basal state, including a variety of upstream regulators, post-translational modifications, and important structural domains that confer the unique properties of CPEB3. Collectively, this review offers a comprehensive view of the regulatory layers that allow a pathway for CPEB3’s maintenance of translational control that guides the necessary protein changes required for the establishment and maintenance of lasting synaptic plasticity and ultimately, long term learning and memory.