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Open Access Green as soon as Postprint is submitted to ZB.
Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition.
Nat. Neurosci. 18, 239-251 (2015)
Neddylation is a ubiquitylation-like pathway that controls cell cycle and proliferation by covalently conjugating Nedd8 to specific targets. However, its role in neurons, nonreplicating postmitotic cells, remains unexplored. Here we report that Nedd8 conjugation increased during postnatal brain development and is active in mature synapses, where many proteins are neddylated. We show that neddylation controls spine development during neuronal maturation and spine stability in mature neurons. We found that neddylated PSD-95 was present in spines and that neddylation on Lys202 of PSD-95 is required for the proactive role of the scaffolding protein in spine maturation and synaptic transmission. Finally, we developed Nae1(CamKIIα-CreERT2) mice, in which neddylation is conditionally ablated in adult excitatory forebrain neurons. These mice showed synaptic loss, impaired neurotransmission and severe cognitive deficits. In summary, our results establish neddylation as an active post-translational modification in the synapse regulating the maturation, stability and function of dendritic spines.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Long-term Potentiation; Dendritic Spines; Synaptic Plasticity; In-vivo; Postsynaptic Density-95; Psd-95; Ubiquitin; Proteins; Filopodia; Nedd8
ISSN (print) / ISBN
1097-6256
e-ISSN
1546-1726
Journal
Nature Neuroscience
Quellenangaben
Volume: 18,
Issue: 2,
Pages: 239-251
Publisher
Nature Publishing Group
Publishing Place
New York
Non-patent literature
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Reviewing status
Peer reviewed