Molecular characterization and comparison of the components and multiprotein complexes in the postsynaptic proteome.
Characterization of the composition of the postsynaptic proteome (PSP) provides a framework for understanding the overall organization and function of the synapse in normal and pathological conditions. We have identified 698 proteins from the postsynaptic terminal of mouse CNS synapses using a series of purification strategies and analysis by liquid chromatography tandem mass spectrometry and large-scale immunoblotting. Some 620 proteins were found in purified postsynaptic densities (PSDs), nine in AMPA-receptor immuno-purifications, 100 in isolates using an antibody against the NMDA receptor subunit NR1, and 170 by peptide-affinity purification of complexes with the C-terminus of NR2B. Together, the NR1 and NR2B complexes contain 186 proteins, collectively referred to as membrane-associated guanylate kinase-associated signalling complexes. We extracted data from six other synapse proteome experiments and combined these with our data to provide a consensus on the composition of the PSP. In total, 1124 proteins are present in the PSP, of which 466 were validated by their detection in two or more studies, forming what we have designated the Consensus PSD. These synapse proteome data sets offer a basis for future research in synaptic biology and will provide useful information in brain disease and mental disorder studies.
Collins
Mark O
MO
Genes to Cognition, The Wellcome Trust Sanger Institute, Hinxton, UK.
Husi
Holger
H
Yu
Lu
L
Brandon
Julia M
JM
Anderson
Chris N G
CN
Blackstock
Walter P
WP
Choudhary
Jyoti S
JS
Grant
Seth G N
SG
D000818:Animals; D001923:Brain Chemistry; D002853:Chromatography, Liquid; D051528:Guanylate Kinases / Q000032:analysis / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D046912:Multiprotein Complexes / Q000032:analysis*; D009419:Nerve Tissue Proteins / Q000032:analysis* / Q000145:classification; D020543:Proteome / Q000032:analysis / Q000737:chemistry*; D013569:Synapses / Q000737:chemistry*
D046912:Multiprotein Complexes; D009419:Nerve Tissue Proteins; D020543:Proteome; D051528:Guanylate Kinases