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Artículo

Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition

Vogl, Annette M.; Brockmann, Marisa M.; Giusti, Sebastian AlejandroIcon ; MacCarrone, Giuseppina; Vercelli, Claudia AlejandraIcon ; Bauder, Corinna A.; Richter, Julia S.; Roselli, Francesco; Hafner, Anne-Sophie; Dedic, Nina; Wotjak, Carsten T.; Vogt Weisenhorn, Daniela M.; Choquet, Daniel; Turck, Christoph W.; Stein, Valentin; Deussing, Jan M.; Refojo, DamianIcon
Fecha de publicación: 02/2015
Editorial: Nature Publishing Group
Revista: Nature Neuroscience.
ISSN: 1097-6256
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Otras Ciencias Biológicas

Resumen

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.
Palabras clave: Neddylation , Dendritic Spines , Synapses , Ubiquitin Like Proteins
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/39796
DOI: http://dx.doi.org/10.1038/nn.3912
URL: https://www.nature.com/articles/nn.3912
Colecciones
Articulos(IBIOBA - MPSP)
Articulos de INST. D/INV.EN BIOMED.DE BS AS-CONICET-INST. PARTNER SOCIEDAD MAX PLANCK
Citación
Vogl, Annette M.; Brockmann, Marisa M.; Giusti, Sebastian Alejandro; MacCarrone, Giuseppina; Vercelli, Claudia Alejandra; et al.; Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition; Nature Publishing Group; Nature Neuroscience.; 18; 2; 2-2015; 239-251
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