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The Synaptonuclear Messenger RNF10 Acts as an Architect of Neuronal Morphology

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Abstract

The Ring Finger Protein 10 [RNF10] is a novel synapse-to-nucleus signaling protein that specifically links activation of synaptic NMDA receptors to modulation of gene expression. RNF10 dissociation from the GluN2A subunit of the NMDA receptor represents the first step of its synaptonuclear transport and it is followed by an importin-dependent translocation into the nucleus. Here, we have identified protein kinase C [PKC]-dependent phosphorylation of RNF10 Ser31 as a key step for RNF10 detachment from NMDA receptor and its subsequent trafficking to the nucleus. We show that pSer31-RNF10 plays a role both in synaptonuclear signaling and in neuronal morphology. In particular, the prevention of Ser31 RNF10 phosphorylation induces a decrease in spine density, neuronal branching, and CREB signaling, while opposite effects are obtained by mimicking a stable RNF10 phosphorylation at Ser31. Overall, these results add novel information about the functional and structural role of synaptonuclear protein messengers in shaping dendritic architecture in hippocampal neurons.

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Acknowledgments

The authors are thankful to Anna Grassi, Francesco Tonolini, and Marta Ornaghi for their technical support.

Funding

DM is supported by DFG grants SFB1158 and FOR2325. DM is a member of the Excellence Cluster Cell Networks at Heidelberg University. This work was supported by the Italian Ministry of University and Research [PRIN 2015N4FKJ4 to MDL], Joint programme—Neurodegenerative disease research project STAD and by MIUR Progetto Eccellenza.

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  1. Nicolò Carrano and Tanmoy Samaddar contributed equally to this work and are listed alphabetically

Authors and Affiliations

  1. Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti 9, 20133, Milan, Italy

    Nicolò Carrano, Tanmoy Samaddar, Electra Brunialti, Luca Franchini, Elena Marcello, Monica Di Luca & Fabrizio Gardoni

  2. Department of Oncology and Hemato-Oncology, University of Milan, Via Balzaretti 9, 20133, Milan, Italy

    Paolo Ciana

  3. Department of Neurobiology, Interdisciplinary Centre for Neurosciences [IZN], Heidelberg University, INF, 366 69120, Heidelberg, Germany

    Daniela Mauceri

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  1. Nicolò Carrano
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Correspondence to Fabrizio Gardoni.

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Carrano, N., Samaddar, T., Brunialti, E. et al. The Synaptonuclear Messenger RNF10 Acts as an Architect of Neuronal Morphology. Mol Neurobiol 56, 7583–7593 (2019). https://doi.org/10.1007/s12035-019-1631-1

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