Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition

Autores
Vogl, Annette M.; Brockmann, Marisa M.; Giusti, Sebastian Alejandro; MacCarrone, Giuseppina; Vercelli, Claudia Alejandra; 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
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
Fil: Vogl, Annette M.. Instituto Max Planck de Psiquiatria de Munich; Alemania
Fil: Brockmann, Marisa M.. Instituto Max Planck de Psiquiatria de Munich; Alemania
Fil: Giusti, Sebastian Alejandro. Instituto Max Planck de Psiquiatria de Munich; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: MacCarrone, Giuseppina. Instituto Max Planck de Psiquiatria de Munich; Alemania
Fil: Vercelli, Claudia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Bauder, Corinna A.. Instituto Max Planck de Psiquiatria de Munich; Alemania
Fil: Richter, Julia S.. Instituto Max Planck de Psiquiatria de Munich; Alemania. Instituto Max Planck de Psiquiatria de Munich; Alemania
Fil: Roselli, Francesco. Universita Degli Studi Di Bari; Italia
Fil: Hafner, Anne-Sophie. Universite de Bordeaux; Francia
Fil: Dedic, Nina. Instituto Max Planck de Psiquiatria de Munich; Alemania
Fil: Wotjak, Carsten T.. Instituto Max Planck de Psiquiatria de Munich; Alemania
Fil: Vogt Weisenhorn, Daniela M.. Institute Of Developmental Genetics; Alemania
Fil: Choquet, Daniel. Universite de Bordeaux; Francia
Fil: Turck, Christoph W.. Instituto Max Planck de Psiquiatria de Munich; Alemania
Fil: Stein, Valentin. Universitaet Bonn; Alemania
Fil: Deussing, Jan M.. Instituto Max Planck de Psiquiatria de Munich; Alemania
Fil: Refojo, Damian. Instituto Max Planck de Psiquiatria de Munich; Alemania
Materia
Neddylation
Dendritic Spines
Synapses
Ubiquitin Like Proteins
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/39796
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/39796
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognitionVogl, Annette M.Brockmann, Marisa M.Giusti, Sebastian AlejandroMacCarrone, GiuseppinaVercelli, Claudia AlejandraBauder, Corinna A.Richter, Julia S.Roselli, FrancescoHafner, Anne-SophieDedic, NinaWotjak, Carsten T.Vogt Weisenhorn, Daniela M.Choquet, DanielTurck, Christoph W.Stein, ValentinDeussing, Jan M.Refojo, DamianNeddylationDendritic SpinesSynapsesUbiquitin Like Proteinshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Neddylation 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.Fil: Vogl, Annette M.. Instituto Max Planck de Psiquiatria de Munich; AlemaniaFil: Brockmann, Marisa M.. Instituto Max Planck de Psiquiatria de Munich; AlemaniaFil: Giusti, Sebastian Alejandro. Instituto Max Planck de Psiquiatria de Munich; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: MacCarrone, Giuseppina. Instituto Max Planck de Psiquiatria de Munich; AlemaniaFil: Vercelli, Claudia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; ArgentinaFil: Bauder, Corinna A.. Instituto Max Planck de Psiquiatria de Munich; AlemaniaFil: Richter, Julia S.. Instituto Max Planck de Psiquiatria de Munich; Alemania. Instituto Max Planck de Psiquiatria de Munich; AlemaniaFil: Roselli, Francesco. Universita Degli Studi Di Bari; ItaliaFil: Hafner, Anne-Sophie. Universite de Bordeaux; FranciaFil: Dedic, Nina. Instituto Max Planck de Psiquiatria de Munich; AlemaniaFil: Wotjak, Carsten T.. Instituto Max Planck de Psiquiatria de Munich; AlemaniaFil: Vogt Weisenhorn, Daniela M.. Institute Of Developmental Genetics; AlemaniaFil: Choquet, Daniel. Universite de Bordeaux; FranciaFil: Turck, Christoph W.. Instituto Max Planck de Psiquiatria de Munich; AlemaniaFil: Stein, Valentin. Universitaet Bonn; AlemaniaFil: Deussing, Jan M.. Instituto Max Planck de Psiquiatria de Munich; AlemaniaFil: Refojo, Damian. Instituto Max Planck de Psiquiatria de Munich; AlemaniaNature Publishing Group2015-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/39796Vogl, 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; 239-2511097-6256CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1038/nn.3912info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/nn.3912info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:16:43Zoai:ri.conicet.gov.ar:11336/39796instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:16:43.307CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition
title Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition
spellingShingle Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition
Vogl, Annette M.
Neddylation
Dendritic Spines
Synapses
Ubiquitin Like Proteins
title_short Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition
title_full Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition
title_fullStr Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition
title_full_unstemmed Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition
title_sort Neddylation inhibition impairs spine development, destabilizes synapses and deteriorates cognition
dc.creator.none.fl_str_mv Vogl, Annette M.
Brockmann, Marisa M.
Giusti, Sebastian Alejandro
MacCarrone, Giuseppina
Vercelli, Claudia Alejandra
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
author Vogl, Annette M.
author_facet Vogl, Annette M.
Brockmann, Marisa M.
Giusti, Sebastian Alejandro
MacCarrone, Giuseppina
Vercelli, Claudia Alejandra
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
author_role author
author2 Brockmann, Marisa M.
Giusti, Sebastian Alejandro
MacCarrone, Giuseppina
Vercelli, Claudia Alejandra
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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Neddylation
Dendritic Spines
Synapses
Ubiquitin Like Proteins
topic Neddylation
Dendritic Spines
Synapses
Ubiquitin Like Proteins
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv 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.
Fil: Vogl, Annette M.. Instituto Max Planck de Psiquiatria de Munich; Alemania
Fil: Brockmann, Marisa M.. Instituto Max Planck de Psiquiatria de Munich; Alemania
Fil: Giusti, Sebastian Alejandro. Instituto Max Planck de Psiquiatria de Munich; Alemania. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: MacCarrone, Giuseppina. Instituto Max Planck de Psiquiatria de Munich; Alemania
Fil: Vercelli, Claudia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación en Biomedicina de Buenos Aires - Instituto Partner de la Sociedad Max Planck; Argentina
Fil: Bauder, Corinna A.. Instituto Max Planck de Psiquiatria de Munich; Alemania
Fil: Richter, Julia S.. Instituto Max Planck de Psiquiatria de Munich; Alemania. Instituto Max Planck de Psiquiatria de Munich; Alemania
Fil: Roselli, Francesco. Universita Degli Studi Di Bari; Italia
Fil: Hafner, Anne-Sophie. Universite de Bordeaux; Francia
Fil: Dedic, Nina. Instituto Max Planck de Psiquiatria de Munich; Alemania
Fil: Wotjak, Carsten T.. Instituto Max Planck de Psiquiatria de Munich; Alemania
Fil: Vogt Weisenhorn, Daniela M.. Institute Of Developmental Genetics; Alemania
Fil: Choquet, Daniel. Universite de Bordeaux; Francia
Fil: Turck, Christoph W.. Instituto Max Planck de Psiquiatria de Munich; Alemania
Fil: Stein, Valentin. Universitaet Bonn; Alemania
Fil: Deussing, Jan M.. Instituto Max Planck de Psiquiatria de Munich; Alemania
Fil: Refojo, Damian. Instituto Max Planck de Psiquiatria de Munich; Alemania
description 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.
publishDate 2015
dc.date.none.fl_str_mv 2015-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/39796
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
1097-6256
CONICET Digital
CONICET
url http://hdl.handle.net/11336/39796
identifier_str_mv 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
1097-6256
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1038/nn.3912
info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/nn.3912
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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