Characterization of the proteome, diseases and evolution of the human postsynaptic density (original) (raw)

Nature Neuroscience volume 14, pages 19–21 (2011)Cite this article

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Abstract

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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Acknowledgements

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.

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Author notes

  1. Àlex Bayés and Louie N van de Lagemaat: These authors contributed equally to this work.

Authors and Affiliations

  1. Genes to Cognition Programme, Wellcome Trust Sanger Institute, Genome Campus, Hinxton, Cambridgeshire, UK
    Àlex Bayés, Louie N van de Lagemaat, Mike D R Croning & Seth G N Grant
  2. Proteomic Mass Spectrometry, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.,
    Mark O Collins & Jyoti S Choudhary
  3. Division of Clinical Neuroscience, Edinburgh University, Edinburgh, UK
    Ian R Whittle

Authors

  1. Àlex Bayés
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  2. Louie N van de Lagemaat
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  3. Mark O Collins
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  4. Mike D R Croning
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  5. Ian R Whittle
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  6. Jyoti S Choudhary
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  7. Seth G N Grant
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Contributions

I.R.W. provided brain samples. A.B., M.O.C. and J.S.C. performed proteomic analysis. A.B. performed OMIM, ICD-10 and evolutionary analyses. L.N.v.L. performed network and enrichment analyses. M.D.R.C. integrated data into G2Cdb. L.N.v.L., M.D.R.C., M.O.C., A.B. and S.G.N.G. wrote the manuscript.

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Correspondence toSeth G N Grant.

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The authors declare no competing financial interests.

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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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