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Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition

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Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition. / Vogl, Annette M; Brockmann, Marisa M; Giusti, Sebastian A; Maccarrone, Giuseppina; Vercelli, Claudia A; 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, Damian.

In: NAT NEUROSCI, Vol. 18, No. 2, 02.2015, p. 239-51.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Vogl, AM, Brockmann, MM, Giusti, SA, Maccarrone, G, Vercelli, CA, Bauder, CA, Richter, JS, Roselli, F, Hafner, A-S, Dedic, N, Wotjak, CT, Vogt-Weisenhorn, DM, Choquet, D, Turck, CW, Stein, V, Deussing, JM & Refojo, D 2015, 'Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition', NAT NEUROSCI, vol. 18, no. 2, pp. 239-51. https://doi.org/10.1038/nn.3912

APA

Vogl, A. M., Brockmann, M. M., Giusti, S. A., Maccarrone, G., Vercelli, C. A., Bauder, C. A., Richter, J. S., Roselli, F., Hafner, A-S., Dedic, N., Wotjak, C. T., Vogt-Weisenhorn, D. M., Choquet, D., Turck, C. W., Stein, V., Deussing, J. M., & Refojo, D. (2015). Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition. NAT NEUROSCI, 18(2), 239-51. https://doi.org/10.1038/nn.3912

Vancouver

Vogl AM, Brockmann MM, Giusti SA, Maccarrone G, Vercelli CA, Bauder CA et al. Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition. NAT NEUROSCI. 2015 Feb;18(2):239-51. https://doi.org/10.1038/nn.3912

Bibtex

@article{c5647a2044b641f4af5cefb73313a34a,
title = "Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition",
abstract = "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. ",
keywords = "Animals, Behavior, Animal/physiology, Brain/growth & development, Cognition Disorders/metabolism, Dendritic Spines/physiology, Disks Large Homolog 4 Protein, Guanylate Kinases/physiology, Membrane Proteins/physiology, Mice, Mice, Inbred C57BL, Mice, Knockout, NEDD8 Protein, Rats, Rats, Sprague-Dawley, Synapses/physiology, Synaptic Transmission/physiology, Ubiquitin-Activating Enzymes/genetics, Ubiquitins/antagonists & inhibitors",
author = "Vogl, {Annette M} and Brockmann, {Marisa M} and Giusti, {Sebastian A} and Giuseppina Maccarrone and Vercelli, {Claudia A} and Bauder, {Corinna A} and Richter, {Julia S} and Francesco Roselli and Anne-Sophie Hafner and Nina Dedic and Wotjak, {Carsten T} and Vogt-Weisenhorn, {Daniela M} and Daniel Choquet and Turck, {Christoph W} and Valentin Stein and Deussing, {Jan M} and Damian Refojo",
year = "2015",
month = feb,
doi = "10.1038/nn.3912",
language = "English",
volume = "18",
pages = "239--51",
journal = "NAT NEUROSCI",
issn = "1097-6256",
publisher = "NATURE PUBLISHING GROUP",
number = "2",

}

RIS

TY - JOUR

T1 - Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition

AU - Vogl, Annette M

AU - Brockmann, Marisa M

AU - Giusti, Sebastian A

AU - Maccarrone, Giuseppina

AU - Vercelli, Claudia A

AU - Bauder, Corinna A

AU - Richter, Julia S

AU - Roselli, Francesco

AU - Hafner, Anne-Sophie

AU - Dedic, Nina

AU - Wotjak, Carsten T

AU - Vogt-Weisenhorn, Daniela M

AU - Choquet, Daniel

AU - Turck, Christoph W

AU - Stein, Valentin

AU - Deussing, Jan M

AU - Refojo, Damian

PY - 2015/2

Y1 - 2015/2

N2 - 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.

AB - 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.

KW - Animals

KW - Behavior, Animal/physiology

KW - Brain/growth & development

KW - Cognition Disorders/metabolism

KW - Dendritic Spines/physiology

KW - Disks Large Homolog 4 Protein

KW - Guanylate Kinases/physiology

KW - Membrane Proteins/physiology

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - NEDD8 Protein

KW - Rats

KW - Rats, Sprague-Dawley

KW - Synapses/physiology

KW - Synaptic Transmission/physiology

KW - Ubiquitin-Activating Enzymes/genetics

KW - Ubiquitins/antagonists & inhibitors

U2 - 10.1038/nn.3912

DO - 10.1038/nn.3912

M3 - SCORING: Journal article

C2 - 25581363

VL - 18

SP - 239

EP - 251

JO - NAT NEUROSCI

JF - NAT NEUROSCI

SN - 1097-6256

IS - 2

ER -