Spatiotemporal profile of postsynaptic interactomes integrates components of complex brain disorders.

Nat Neurosci 2017 Aug 26;20(8):1150-1161. Epub 2017 Jun 26.

Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California, USA.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1038/nn.4594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645082PMC
August 2017
58 Reads

Publication Analysis

Top Keywords

risk factors
8
brain disorders
8
disease risk
8
complex brain
8
proteins vivo
4
vivo interactomes
4
nodes alter
4
2876 proteins
4
isolated 2876
4
connected nodes
4
interactomes determined
4
mutations highly
4
protein domain
4
highly connected
4
determined protein
4
alter protein-protein
4
distributed spatiotemporal
4
immunopurification proteomics
4
protein complexes
4
modulating macromolecular
4

References

(Supplied by CrossRef)
Article in Nat. Neurosci.
A Bayés et al.
Nat. Neurosci. 2011
Article in J. Neurochem.
MO Collins et al.
J. Neurochem. 2006
Article in Sci. Signal.
MP Coba et al.
Sci. Signal. 2009
Article in J. Biol. Chem.
MO Collins et al.
J. Biol. Chem. 2005
Article in Nat. Neurosci.
H Husi et al.
Nat. Neurosci. 2000
Article in Science
T Pawson et al.
Science 1997
Article in Science
JD Scott et al.
Science 2009
Article in Cold Spring Harb. Perspect. Biol.
M Sheng et al.
Cold Spring Harb. Perspect. Biol. 2011
Article in Science
HC Kornau et al.
Science 1995
Article in Mol. Syst. Biol.
E Fernández et al.
Mol. Syst. Biol. 2009
Article in J. Cell Biol.
E Kim et al.
J. Cell Biol. 1997

Similar Publications