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.
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DISC1 anchors many proteins and regulates their functional localization and molecular interactions.
“DISC1 anchors many proteins and thus regulates their functional localization and molecular interactions124.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [124]
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- Authors
- Camargo, L. M., Collura, V, Rain, J.-C., Mizuguchi, K., Hermjakob, H., Kerrien, S., Bonnert, T. P., Whiting, P. J., & Brandon, N. J.
- Affiliations
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Hybrigenics (France) (FR)
- University of Cambridge (GB)
- European Bioinformatics Institute (GB)
- MSD (UK) Limited (United Kingdom) (GB)
- Corresponding author
- Camargo, L M
- Venue
- Molecular Psychiatry
- Published
- 2006-10-17
- Volume
- 12
- Issue
- 1
- Pages
- 74-86
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2049733177
- Cited by
- 405
- References
- 77
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 9 · 2023: 5 · 2022: 11 · 2021: 16 · 2020: 15 · 2019: 16 · 2018: 12 · 2017: 19 · 2016: 21 · 2015: 26 · 2014: 27 · 2013: 25 · 2012: 37
- FWCI
- 16.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- disrupted-in-schizophrenia 1, protein-protein interaction, schizophrenia risk genes, dysbindin, DTNBP1, synaptic proteins, cognitive impairment, cytoskeletal stability, intracellular transport, cell cycle, synaptic dysfunction
- MeSH terms
- Dysbindin, Biological Transport, Carrier Proteins, Cell Division, Cognition, Cytoskeleton, Humans, Nerve Tissue Proteins, Risk Factors, Schizophrenia, Synapses, Two-Hybrid System Techniques, Dystrophin-Associated Proteins
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