Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia
pmid: 17043677
Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia
Disrupted in Schizophrenia 1 (DISC1) is a schizophrenia risk gene associated with cognitive deficits in both schizophrenics and the normal ageing population. In this study, we have generated a network of protein-protein interactions (PPIs) around DISC1. This has been achieved by utilising iterative yeast-two hybrid (Y2H) screens, combined with detailed pathway and functional analysis. This so-called 'DISC1 interactome' contains many novel PPIs and provides a molecular framework to explore the function of DISC1. The network implicates DISC1 in processes of cytoskeletal stability and organisation, intracellular transport and cell-cycle/division. In particular, DISC1 looks to have a PPI profile consistent with that of an essential synaptic protein, which fits well with the underlying molecular pathology observed at the synaptic level and the cognitive deficits seen behaviourally in schizophrenics. Utilising a similar approach with dysbindin (DTNBP1), a second schizophrenia risk gene, we show that dysbindin and DISC1 share common PPIs suggesting they may affect common biological processes and that the function of schizophrenia risk genes may converge.
- College of New Jersey United States
- University of Cambridge United Kingdom
- European Bioinformatics Institute United Kingdom
- Merck & Co. United States
- European Molecular Biology Laboratory Germany
Dysbindin, Biological Transport, Nerve Tissue Proteins, Cognition, Risk Factors, Two-Hybrid System Techniques, Dystrophin-Associated Proteins, Synapses, Schizophrenia, Humans, Carrier Proteins, Cell Division, Cytoskeleton
Dysbindin, Biological Transport, Nerve Tissue Proteins, Cognition, Risk Factors, Two-Hybrid System Techniques, Dystrophin-Associated Proteins, Synapses, Schizophrenia, Humans, Carrier Proteins, Cell Division, Cytoskeleton
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