Title |
Spatiotemporal profile of postsynaptic interactomes integrates components of complex brain disorders
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Published in |
Nature Neuroscience, June 2017
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DOI | 10.1038/nn.4594 |
Pubmed ID | |
Authors |
Jing Li, Wangshu Zhang, Hui Yang, Daniel P Howrigan, Brent Wilkinson, Tade Souaiaia, Oleg V Evgrafov, Giulio Genovese, Veronica A Clementel, Jennifer C Tudor, Ted Abel, James A Knowles, Benjamin M Neale, Kai Wang, Fengzhu Sun, Marcelo P Coba |
Abstract |
The postsynaptic density (PSD) contains a collection of scaffold proteins used for assembling synaptic signaling complexes. However, it is not known how the core-scaffold machinery associates in protein-interaction networks or how proteins encoded by genes involved in complex brain disorders are distributed through spatiotemporal protein complexes. Here using immunopurification, proteomics and bioinformatics, we isolated 2,876 proteins across 41 in vivo interactomes and determined their protein domain composition, correlation to gene expression levels and developmental integration to the PSD. We defined clusters for enrichment of schizophrenia, autism spectrum disorders, developmental delay and intellectual disability risk factors at embryonic day 14 and adult PSD in mice. Mutations in highly connected nodes alter protein-protein interactions modulating macromolecular complexes enriched in disease risk candidates. These results were integrated into a software platform, Synaptic Protein/Pathways Resource (SyPPRes), enabling the prioritization of disease risk factors and their placement within synaptic protein interaction networks. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 5 | 17% |
United Kingdom | 3 | 10% |
Italy | 1 | 3% |
Netherlands | 1 | 3% |
Belgium | 1 | 3% |
Egypt | 1 | 3% |
Colombia | 1 | 3% |
Ireland | 1 | 3% |
France | 1 | 3% |
Other | 1 | 3% |
Unknown | 14 | 47% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 18 | 60% |
Scientists | 9 | 30% |
Science communicators (journalists, bloggers, editors) | 2 | 7% |
Practitioners (doctors, other healthcare professionals) | 1 | 3% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 1 | <1% |
Unknown | 187 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 40 | 21% |
Student > Ph. D. Student | 39 | 21% |
Student > Master | 18 | 10% |
Professor > Associate Professor | 11 | 6% |
Professor | 9 | 5% |
Other | 29 | 15% |
Unknown | 42 | 22% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 44 | 23% |
Biochemistry, Genetics and Molecular Biology | 28 | 15% |
Agricultural and Biological Sciences | 27 | 14% |
Medicine and Dentistry | 15 | 8% |
Unspecified | 4 | 2% |
Other | 18 | 10% |
Unknown | 52 | 28% |