Topic: RNF10

Synaptonuclear signalling pathways have been implicated in long term plasticity events. Nonetheless, their role in regulating cognitive behavior remains to be clarified. Here, we demonstrated that RNF10-mediated synapse-to-nucleus signaling, linking activation of synaptic NMDARs to specific transcriptional programmes in the dorsal CA1, is necessary for cognitive flexibility. In vivo RNF10 downregulation, through gene deletion and silencing, induced, specifically in CA1, alterations of both long-term potentiation and dendritic spines’ structure. At behavioral level, RNF10 downregulation suppres

RNF10 is a protein with multiple cellular functions. It has been described as a E3-Ubiquitin ligase, with a key quality-control role during the initiation of translation in the early regulatory ribosome ubiquitylation (RQC). In addition, RNF10 plays in neurons a role as a synaptonuclear messenger, involved in the NMDA receptors (NMDAR) signaling cascade. RNF10 binds to the C-terminal region of the GluN2A subunit of the NMDAR and its translocation from the synapse to the nucleus translates synaptic NMDAR activation into gene expression changes. RNF10 is crucial in the physiology of the neurons,