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

Giralt, A., Brito, V., Chevy, Q., Simonnet, C., Otsu, Y., Cifuentes-Diaz, C., de Pins, B., Coura, R., Alberch, J., Gines, S., Poncer, J. C., Girault, J. A. (May 2017) Pyk2 modulates hippocampal excitatory synapses and contributes to cognitive deficits in a Huntington's disease model. Nature Communications, 8. p. 15592. ISSN 2041-1723

URL: https://www.ncbi.nlm.nih.gov/pubmed/28555636
DOI: 10.1038/ncomms15592

Abstract

R6/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.

Item Type: Paper
Subjects: organism description > animal behavior > perception > cognition
organs, tissues, organelles, cell types and functions > tissues types and functions > hippocampus
diseases & disorders > cancer > cancer types > huntington's disease
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse
CSHL Authors:
Communities: CSHL labs > Kepecs lab
Depositing User: Matt Covey
Date: 30 May 2017
Date Deposited: 08 Jun 2017 19:13
Last Modified: 21 Jun 2017 19:56
PMCID: PMC5459995
Related URLs:
URI: http://repository.cshl.edu/id/eprint/34922

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