title: Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia.
abstract: 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.
authors.affiliation: Merck Research Labs, Merck & Co., Boston, MA 02115, USA. miguel_camargo@merck.com
authors.forename: L M
authors.initials: LM
authors.lastname: Camargo
authors.forename: V
authors.initials: V
authors.lastname: Collura
authors.forename: J-C
authors.initials: JC
authors.lastname: Rain
authors.forename: K
authors.initials: K
authors.lastname: Mizuguchi
authors.forename: H
authors.initials: H
authors.lastname: Hermjakob
authors.forename: S
authors.initials: S
authors.lastname: Kerrien
authors.forename: T P
authors.initials: TP
authors.lastname: Bonnert
authors.forename: P J
authors.initials: PJ
authors.lastname: Whiting
authors.forename: N J
authors.initials: NJ
authors.lastname: Brandon
mesh_terms: D001692:Biological Transport / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D003071:Cognition / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D012307:Risk Factors; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology*; D020798:Two-Hybrid System Techniques
chemical_list: D002352:Carrier Proteins; C412476:DISC1 protein, human; C432416:DTNBP1 protein, human; D000074765:Dysbindin; D049029:Dystrophin-Associated Proteins; D009419:Nerve Tissue Proteins