We isolated the postsynaptic density from human neocortex (hPSD) and identified 1,461 proteins. hPSD mutations cause 133 neurological and psychiatric diseases and were enriched in cognitive, affective and motor phenotypes underpinned by sets of genes. Strong protein sequence conservation in mammalian lineages, particularly in hub proteins, indicates conserved function and organization in primate and rodent models. The hPSD is an important structure for nervous system disease and behavior.
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We thank C.P. Ponting, P.J. Brophy, R.A.W. Frank, N.H. Komiyama, M.V. Kopanitsa, T.J. Ryan and members of the Genes to Cognition Programme for critical comments on the manuscript and for discussions. We thank the tissue donors, without whom this study would have been impossible. A.B. is supported by EMBO and the European Commission. L.N.v.L., M.O.C., M.D.R.C., J.S.C. and S.G.N.G. are supported by the Wellcome Trust. I.R.W. is supported by Scottish Higher Education Funding Council and by grants from the Medical Research Council, the US National Institutes of Health and the Melville Trust.
The authors declare no competing financial interests.
Supplementary Figures 1–4 and Supplementary Methods (PDF 740 kb)
Information about Biological Samples. (XLS 28 kb)
Protein Identifications and Proteomic Data. (XLS 445 kb)
Summary of OMIM Diseases. (XLS 19 kb)
OMIM Diseases Identified Among Total hPSD Genes. (XLS 141 kb)
Human Neural Phenotype gene set enrichment analysis. (XLS 93 kb)
Brain datasets used in phenotype enrichment analysis. (XLS 327 kb)
Mammalian Neural Phenotype gene set enrichment Analysis. (XLS 187 kb)
Comparison of dN/dS between Genome and hPSD. (XLS 10375 kb)
Mouse and Human Brain Datasets dN/dS Analysis. (XLS 740 kb)
dN/dS Values for genes expressed in human neurons classified by cellular component. (XLS 847 kb)
Analysis of dN/dS on Hub, non-Hub and TAP-PSD-95 proteins. (XLS 135 kb)
Mouse to Human dN/dS Values in hPSD and Other Organelle Proteomes. (XLS 3289 kb)
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Bayés, À., van de Lagemaat, L., Collins, M. et al. Characterization of the proteome, diseases and evolution of the human postsynaptic density. Nat Neurosci 14, 19–21 (2011). https://doi.org/10.1038/nn.2719
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