From the Cover: Disrupted-in-Schizophrenia-1 (DISC-1): Mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth (original) (raw)
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- Tomoda, Toshifumi ;
- Kleiderlein, John ;
- Kamiya, Atsushi ;
- Bord, Lyuda ;
- Fujii, Kumiko ;
- Okawa, Masako ;
- Yamada, Naoto ;
- Hatten, Mary E. ;
- Snyder, Solomon H. ;
- Ross, Christopher A. ;
- Sawa, Akira
Abstract
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.
Publication:
Proceedings of the National Academy of Science
Pub Date:
January 2003
DOI:
Bibcode:
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- From the Cover