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Molecular Brain
Published in: Molecular Brain 1/2014

Open Access 01-12-2014 | Research

Human post-mortem synapse proteome integrity screening for proteomic studies of postsynaptic complexes

Authors: Àlex Bayés, Mark O Collins, Clare M Galtrey, Clémence Simonnet, Marcia Roy, Mike DR Croning, Gemma Gou, Louie N van de Lagemaat, David Milward, Ian R Whittle, Colin Smith, Jyoti S Choudhary, Seth GN Grant

Published in: Molecular Brain | Issue 1/2014

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Abstract

Background

Synapses are fundamental components of brain circuits and are disrupted in over 100 neurological and psychiatric diseases. The synapse proteome is physically organized into multiprotein complexes and polygenic mutations converge on postsynaptic complexes in schizophrenia, autism and intellectual disability. Directly characterising human synapses and their multiprotein complexes from post-mortem tissue is essential to understanding disease mechanisms. However, multiprotein complexes have not been directly isolated from human synapses and the feasibility of their isolation from post-mortem tissue is unknown.

Results

Here we establish a screening assay and criteria to identify post-mortem brain samples containing well-preserved synapse proteomes, revealing that neocortex samples are best preserved. We also develop a rapid method for the isolation of synapse proteomes from human brain, allowing large numbers of post-mortem samples to be processed in a short time frame. We perform the first purification and proteomic mass spectrometry analysis of MAGUK Associated Signalling Complexes (MASC) from neurosurgical and post-mortem tissue and find genetic evidence for their involvement in over seventy human brain diseases.

Conclusions

We have demonstrated that synaptic proteome integrity can be rapidly assessed from human post-mortem brain samples prior to its analysis with sophisticated proteomic methods. We have also shown that proteomics of synapse multiprotein complexes from well preserved post-mortem tissue is possible, obtaining structures highly similar to those isolated from biopsy tissue. Finally we have shown that MASC from human synapses are involved with over seventy brain disorders. These findings should have wide application in understanding the synaptic basis of psychiatric and other mental disorders.
Appendix
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Metadata
Title
Human post-mortem synapse proteome integrity screening for proteomic studies of postsynaptic complexes
Authors
Àlex Bayés
Mark O Collins
Clare M Galtrey
Clémence Simonnet
Marcia Roy
Mike DR Croning
Gemma Gou
Louie N van de Lagemaat
David Milward
Ian R Whittle
Colin Smith
Jyoti S Choudhary
Seth GN Grant
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Brain / Issue 1/2014
Electronic ISSN: 1756-6606
DOI
https://doi.org/10.1186/s13041-014-0088-4

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