Ring finger protein 10 is a novel synaptonuclear messenger encoding activation of NMDA receptors in hippocampus

环指蛋白 10 是一种新型突触核信使,编码激活海马中的 NMDA 受体

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作者:Margarita C Dinamarca, Francesca Guzzetti, Anna Karpova, Dmitry Lim, Nico Mitro, Stefano Musardo, Manuela Mellone, Elena Marcello, Jennifer Stanic, Tanmoy Samaddar, Adeline Burguière, Antonio Caldarelli, Armando A Genazzani, Julie Perroy, Laurent Fagni, Pier Luigi Canonico, Michael R Kreutz, Fabrizi

Abstract

Synapses and nuclei are connected by bidirectional communication mechanisms that enable information transfer encoded by macromolecules. Here, we identified RNF10 as a novel synaptonuclear protein messenger. RNF10 is activated by calcium signals at the postsynaptic compartment and elicits discrete changes at the transcriptional level. RNF10 is enriched at the excitatory synapse where it associates with the GluN2A subunit of NMDA receptors (NMDARs). Activation of synaptic GluN2A-containing NMDARs and induction of long term potentiation (LTP) lead to the translocation of RNF10 from dendritic segments and dendritic spines to the nucleus. In particular, we provide evidence for importin-dependent long-distance transport from synapto-dendritic compartments to the nucleus. Notably, RNF10 silencing prevents the maintenance of LTP as well as LTP-dependent structural modifications of dendritic spines.

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