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  Neddylation regulates excitatory synaptic transmission and plasticity

Brockmann, M. M., Doengi, M., Einsfelder, U., Koerber, N., Refojo, D., & Stein, V. (2019). Neddylation regulates excitatory synaptic transmission and plasticity. Scientific Reports, 9: 17935. doi:10.1038/s41598-019-54182-2.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0005-F8D8-0 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-F8D9-F
Genre: Journal Article

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 Creators:
Brockmann, Marisa M.1, Author              
Doengi, Michael, Author
Einsfelder, Ulf, Author
Koerber, Nils, Author
Refojo, Damian1, 2, Author              
Stein, Valentin3, Author              
Affiliations:
1Max Planck Research Group Molecular Neurobiology (Damian Refojo), Max Planck Institute of Psychiatry, Max Planck Society, ou_1607138              
2Dept. Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Max Planck Society, ou_2035294              
3Max Planck Research Group: Synaptic Receptor Trafficking / Stein, MPI of Neurobiology, Max Planck Society, ou_1113557              

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 Abstract: Post-translational modifications, like phosphorylation, ubiquitylation, and sumoylation, have been shown to impact on synaptic neurotransmission by modifying pre- and postsynaptic proteins and therefore alter protein stability, localization, or protein-protein interactions. Previous studies showed that post-translational modifications are essential during the induction of synaptic plasticity, defined by a major reorganization of synaptic proteins. We demonstrated before that neddylation, a post-translational modification that covalently binds Nedd8 to lysine-residues, strongly affects neuronal maturation and spine stability. We now analysed the consequences of inhibiting neddylation on excitatory synaptic transmission and plasticity, which will help to narrow down possible targets, to make educated guesses, and test specific candidates. Here, we show that acute inhibition of neddylation impacts on synaptic neurotransmission before morphological changes occur. Our data indicate that pre- and postsynaptic proteins are neddylated since the inhibition of neddylation impacts on presynaptic release probability and postsynaptic receptor stabilization. In addition, blocking neddylation during the induction of long-term potentiation and long-term inhibition abolished both forms of synaptic plasticity. Therefore, this study shows the importance of identifying synaptic targets of the neddylation pathway to understand the regulation of synaptic transmission and plasticity.

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 Dates: 2019-11-29
 Publication Status: Published online
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Title: Scientific Reports
  Abbreviation : Sci. Rep.
Source Genre: Journal
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Publ. Info: London, UK : Nature Publishing Group
Pages: - Volume / Issue: 9 Sequence Number: 17935 Start / End Page: - Identifier: ISSN: 2045-2322
CoNE: https://pure.mpg.de/cone/journals/resource/2045-2322