Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington's disease model.

The structure and function of spines and excitatory synapses are under the dynamic control of multiple signalling networks. Although tyrosine phosphorylation is involved, its regulation and importance are not well understood. Here we study the role of Pyk2, a non-receptor calcium-dependent protein-t...

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Autores: Giralt Torroella, Albert, Brito, Verónica, Chevy, Quentin, Simonnet, Clémence, Otsu, Yo, Cifuentes Díaz, Carmen, Pins, Benoit de, Coura, Renata, Alberch i Vié, Jordi, 1959-, Ginés Padrós, Silvia, Poncer, Jean Christophe, Girault, Jean-Antoine
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/112378
Acceso en línea:https://hdl.handle.net/2445/112378
Access Level:acceso abierto
Palabra clave:Corea de Huntington
Malalties neurodegeneratives
Hipocamp (Cervell)
Huntington's chorea
Neurodegenerative Diseases
Hippocampus (Brain)
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spelling Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington's disease model.Giralt Torroella, AlbertBrito, VerónicaChevy, QuentinSimonnet, ClémenceOtsu, YoCifuentes Díaz, CarmenPins, Benoit deCoura, RenataAlberch i Vié, Jordi, 1959-Ginés Padrós, SilviaPoncer, Jean ChristopheGirault, Jean-AntoineCorea de HuntingtonMalalties neurodegenerativesHipocamp (Cervell)Huntington's choreaNeurodegenerative DiseasesHippocampus (Brain)The structure and function of spines and excitatory synapses are under the dynamic control of multiple signalling networks. Although tyrosine phosphorylation is involved, its regulation and importance are not well understood. Here we study the role of Pyk2, a non-receptor calcium-dependent protein-tyrosine kinase highly expressed in the hippocampus. Hippocampal-related learning and CA1 long-term potentiation are severely impaired in Pyk2-deficient mice and are associated with alterations in NMDA receptors, PSD-95 and dendritic spines. In cultured hippocampal neurons, Pyk2 has autophosphorylation-dependent and -independent roles in determining PSD-95 enrichment and spines density. Pyk2 levels are decreased in the hippocampus of individuals with Huntington and in the R6/1 mouse model of the disease. Normalizing Pyk2 levels in the hippocampus of R6/1 mice rescues memory deficits, spines pathology and PSD-95 localization. Our results reveal a role for Pyk2 in spine structure and synaptic function, and suggest that its deficit contributes to Huntington's disease cognitive impairments.Nature Publishing Group2017info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/112378Articles publicats en revistes (Biomedicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1038/ncomms15592Nature Communications, 2017, vol. 8, num. 15592https://doi.org/10.1038/ncomms15592info:eu-repo/grantAgreement/EC/FP7/250349cc-by (c) Giralt Torroella, Albert et al., 2017http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1123782026-05-27T06:46:51Z
dc.title.none.fl_str_mv Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington's disease model.
title Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington's disease model.
spellingShingle Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington's disease model.
Giralt Torroella, Albert
Corea de Huntington
Malalties neurodegeneratives
Hipocamp (Cervell)
Huntington's chorea
Neurodegenerative Diseases
Hippocampus (Brain)
title_short Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington's disease model.
title_full Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington's disease model.
title_fullStr Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington's disease model.
title_full_unstemmed Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington's disease model.
title_sort Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington's disease model.
dc.creator.none.fl_str_mv Giralt Torroella, Albert
Brito, Verónica
Chevy, Quentin
Simonnet, Clémence
Otsu, Yo
Cifuentes Díaz, Carmen
Pins, Benoit de
Coura, Renata
Alberch i Vié, Jordi, 1959-
Ginés Padrós, Silvia
Poncer, Jean Christophe
Girault, Jean-Antoine
author Giralt Torroella, Albert
author_facet Giralt Torroella, Albert
Brito, Verónica
Chevy, Quentin
Simonnet, Clémence
Otsu, Yo
Cifuentes Díaz, Carmen
Pins, Benoit de
Coura, Renata
Alberch i Vié, Jordi, 1959-
Ginés Padrós, Silvia
Poncer, Jean Christophe
Girault, Jean-Antoine
author_role author
author2 Brito, Verónica
Chevy, Quentin
Simonnet, Clémence
Otsu, Yo
Cifuentes Díaz, Carmen
Pins, Benoit de
Coura, Renata
Alberch i Vié, Jordi, 1959-
Ginés Padrós, Silvia
Poncer, Jean Christophe
Girault, Jean-Antoine
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Corea de Huntington
Malalties neurodegeneratives
Hipocamp (Cervell)
Huntington's chorea
Neurodegenerative Diseases
Hippocampus (Brain)
topic Corea de Huntington
Malalties neurodegeneratives
Hipocamp (Cervell)
Huntington's chorea
Neurodegenerative Diseases
Hippocampus (Brain)
description The structure and function of spines and excitatory synapses are under the dynamic control of multiple signalling networks. Although tyrosine phosphorylation is involved, its regulation and importance are not well understood. Here we study the role of Pyk2, a non-receptor calcium-dependent protein-tyrosine kinase highly expressed in the hippocampus. Hippocampal-related learning and CA1 long-term potentiation are severely impaired in Pyk2-deficient mice and are associated with alterations in NMDA receptors, PSD-95 and dendritic spines. In cultured hippocampal neurons, Pyk2 has autophosphorylation-dependent and -independent roles in determining PSD-95 enrichment and spines density. Pyk2 levels are decreased in the hippocampus of individuals with Huntington and in the R6/1 mouse model of the disease. Normalizing Pyk2 levels in the hippocampus of R6/1 mice rescues memory deficits, spines pathology and PSD-95 localization. Our results reveal a role for Pyk2 in spine structure and synaptic function, and suggest that its deficit contributes to Huntington's disease cognitive impairments.
publishDate 2017
dc.date.none.fl_str_mv 2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/112378
url https://hdl.handle.net/2445/112378
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1038/ncomms15592
Nature Communications, 2017, vol. 8, num. 15592
https://doi.org/10.1038/ncomms15592
info:eu-repo/grantAgreement/EC/FP7/250349
dc.rights.none.fl_str_mv cc-by (c) Giralt Torroella, Albert et al., 2017
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Giralt Torroella, Albert et al., 2017
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 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 Articles publicats en revistes (Biomedicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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