ausblenden:
Schlagwörter:
Cognitive neuroscience, Neddylation, Synaptic transmission, Spine regulation and structure
Zusammenfassung:
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(CamKll alpha-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.
