Föcking, M and Lopez, Lorna M. and English, J A and Dicker, P and Wolff, A and Brindley, E and Wynne, K and Cagney, G and Cotter, D R (2015) Proteomic and genomic evidence implicates the postsynaptic density in schizophrenia. Molecular Psychiatry, 20 (4). pp. 424-432. ISSN 1359-4184

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Abstract

The postsynaptic density (PSD) contains a complex set of proteins of known relevance to neuropsychiatric disorders, and schizophrenia specifically. We enriched for this anatomical structure, in the anterior cingulate cortex, of 20 schizophrenia samples and 20 controls from the Stanley Medical Research Institute, and used unbiased shotgun proteomics incorporating label-free quantitation to identify differentially expressed proteins. Quantitative investigation of the PSD revealed more than 700 protein identifications and 143 differentially expressed proteins. Prominent among these were altered expression of proteins involved in clathrin-mediated endocytosis (CME) (Dynamin-1, adaptor protein 2) and N-methyl-D-aspartate (NMDA)-interacting proteins such as CYFIP2, SYNPO, SHANK3, ESYT and MAPK3 (all P<0.0015). Pathway analysis of the differentially expressed proteins implicated the cellular processes of endocytosis, long-term potentiation and calcium signaling. Both single-gene and gene-set enrichment analyses in genome-wide association data from the largest schizophrenia sample to date of 13 689 cases and 18 226 controls show significant association of HIST1H1E and MAPK3, and enrichment of our PSD proteome. Taken together, our data provide robust evidence implicating PSD-associated proteins and genes in schizophrenia, and suggest that within the PSD, NMDA-interacting and endocytosis-related proteins contribute to disease pathophysiology.

Item Type:	Article
Keywords:	Proteomic; genomic evidence; implicates; postsynaptic density; schizophrenia;
Academic Unit:	Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	16267
Identification Number:	https://doi.org/10.1038/mp.2014.63
Depositing User:	Lorna Lopez
Date Deposited:	06 Jul 2022 10:57
Journal or Publication Title:	Molecular Psychiatry
Publisher:	Nature Publishing Group
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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