Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/112378
Title: Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington's disease model.
Author: Giralt Torroella, Albert
Brito, Verónica
Chevy, Quentin
Simonnet, Clémence
Otsu, Yo
Cifuentes Díaz, Carmen
Pins, Benoit de
Coura, Renata
Alberch i Vié, Jordi
Ginés Padrós, Silvia
Poncer, Jean Christophe
Girault, Jean Antoine
Keywords: Corea de Huntington
Malalties neurodegeneratives
Hipocamp (Cervell)
Huntington's chorea
Neurodegenerative Diseases
Hippocampus (Brain)
Issue Date: 30-May-2017
Publisher: Nature Publishing Group
Abstract: 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.
Note: Reproducció del document publicat a: https://doi.org/10.1038/ncomms15592
It is part of: Nature Communications, 2017, vol. 8, num. 15592
Related resource: https://doi.org/10.1038/ncomms15592
URI: http://hdl.handle.net/2445/112378
ISSN: 2041-1723
Appears in Collections:Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

Files in This Item:
File Description SizeFormat 
671893.pdf3.64 MBAdobe PDFView/Open


This item is licensed under a Creative Commons License Creative Commons