Integrating synapse proteomics with transcriptional regulation.
The mammalian postsynaptic proteome (PSP) comprises a highly interconnected set of approximately 1,000 proteins. The PSP is organized into macromolecular complexes that have a modular architecture defined by protein interactions and function. Signals initiated by neurotransmitter receptors are integrated by these complexes and their constituent enzymes to orchestrate multiple downstream cellular changes, including transcriptional regulation of genes at the nucleus. Genome wide transcriptome studies are beginning to map the sets of genes regulated by the synapse proteome. Conversely, understanding the transcriptional regulation of genes encoding the synapse proteome will shed light on synapse formation. Mutations that disrupt synapse signalling complexes result in cognitive impairments in mice and humans, and recent evidence indicates that these mutation change gene expression profiles. We discuss the need for global approaches combining genetics, transcriptomics and proteomics in order to understand cognitive function and disruption in diseases.
Valor
L M
LM
Genes to Cognition Programme, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK.
Grant
S G N
SG
D000818:Animals; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D008954:Models, Biological; D040901:Proteomics; D013569:Synapses / Q000378:metabolism*; D049490:Systems Biology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D014157:Transcription Factors