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Disrupted-in-Schizophrenia-1 (DISC-1): Mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth
Open accessAbstract
Disrupted-in-Schizophrenia-1 ( DISC-1 ) is a gene whose mutant truncation is associated with major psychiatric illness with a predominance of schizophrenic symptomatology. We have cloned and characterized rodent DISC-1. DISC-1 expression displays pronounced developmental regulation with the highest levels in late embryonic life when the cerebral cortex develops. In yeast two-hybrid analyses, DISC-1 interacts with a variety of cytoskeletal proteins. One of these, NudE-like (NUDEL), is associated with cortical development and is linked to LIS-1, the disease gene for a form of lissencephaly, a disorder of cortical development. The disease mutant form of DISC-1 fails to bind NUDEL. Expression of mutant, but not wild-type, DISC-1 in PC12 cells reduces neurite extension. As schizophrenia is thought to reflect defects in cortical development that are determined by cytoskeletal protein activities, the cellular disturbances we observe with mutant DISC-1 may be relevant to psychopathologic mechanisms.
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Chung, K. K. K., Zhang, Y., Lim, K. L., Tanaka, Y., Huang, H., Gao, J., Ross, C. A., Dawson, V. L., & Dawson, T. M. (2001) · Nature Medicine · doi:10.1038/nm1001-1144 · Cited by 750
Self-citationCitron binds to PSD-95 at glutamatergic synapses on inhibitory neurons in the hippocampus
Zhang, W., Vazquez, L., Apperson, M., & Kennedy, M. B. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-01-00096.1999 · Cited by 190
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Schizophrenia genes, gene expression, and neuropathology: on the matter of their convergence
Harrison, P. J., & Weinberger, D. R. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001558 · Cited by 2,020
Disrupted-In-Schizophrenia 1 Regulates Integration of Newly Generated Neurons in the Adult Brain
Duan, X., Chang, J. H., Ge, S., Faulkner, R. L., Kim, J. Y., Kitabatake, Y., Liu, X.-B., Yang, C.-H., Jordan, J. D., Ma, D. K., et al. (2007) · Cell · doi:10.1016/j.cell.2007.07.010 · Cited by 611
The genetics of schizophrenia and bipolar disorder: dissecting psychosis
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The DISC locus in psychiatric illness
Chubb, J. E., Bradshaw, N. J., Soares, D. C., Porteous, D. J., & Millar, J. K. (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4002106 · Cited by 542
Metadata
- Authors
- Ozeki, Y., Tomoda, T., Kleiderlein, J., Kamiya, A., Bord, L., Fujii, K., Okawa, M., Yamada, N., Hatten, M. E., Snyder, S. H., Ross, C. A., & Sawa, A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2002-12-27
- Volume
- 100
- Issue
- 1
- Pages
- 289-294
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2036538226
- Cited by
- 392
- References
- 2
- FWCI
- 13.13
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Ozeki, Y., Tomoda, T., Kleiderlein, J., Kamiya, A., Bord, L., Fujii, K., Okawa, M., Yamada, N., Hatten, M. E., Snyder, S. H., Ross, C. A., & Sawa, A. (2003). Disrupted-in-Schizophrenia-1 (DISC-1): Mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0136913100
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
