Meccanismi regolatori della separazione di fase liquido-liquido di CPEB3 ​

The cytoplasmic polyadenylation element binding protein 3 (CPEB3) is involved in the long-term maintenance of memory-related synaptic plasticity by regulating the translation of mRNAs that are locally stored at neuronal synapses. In the basal state, CPEB3 has a repressive role on translation and is localized, together with its target mRNAs, at P bodies through a process of liquid-liquid phase separation (LLPS). LLPS is a process by which proteins and nucleic acids assemble into membrane-less, dynamic, liquid-like condensates held together by relatively weak molecular interactions. Upon synaptic stimulation, CPEB3 is thought to undergo a structural and functional prion-like switch, forming fibrils acting as molecular scaffolds that promote the polyadenylation, and subsequent translation, of its target mRNA. The molecular mechanisms regulating the structural and functional transitions of CPEB3 in long-term memory, and in particular of its LLPS behaviour, are only partially understood. Therefore, this research work aimed at exploring and defining some of the mechanisms regulating CPEB3 LLPS. We focused our analysis on three aspects of this regulation, through a combination of molecular and cellular biology techniques with fluorescence confocal imaging approaches. Our findings identify novel aspects the physiological regulation of the CPEB3 LLPS behaviour, with implications for our understanding of the molecular underpinnings of the long-term maintenance of synaptic memories.