TY - JOUR
T1 - Disrupted-in-Schizophrenia-1 (DISC-1)
T2 - Mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth
AU - Ozeki, Yuji
AU - Tomoda, Toshifumi
AU - Kleiderlein, John
AU - Kamiya, Atsushi
AU - Bord, Lyuda
AU - Fujii, Kumiko
AU - Okawa, Masako
AU - Yamada, Naoto
AU - Hatten, Mary E.
AU - Snyder, Solomon H.
AU - Ross, Christopher A.
AU - Sawa, Akira
PY - 2003/1/7
Y1 - 2003/1/7
N2 - 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.
AB - 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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U2 - 10.1073/pnas.0136913100
DO - 10.1073/pnas.0136913100
M3 - Article
C2 - 12506198
AN - SCOPUS:0037422609
SN - 0027-8424
VL - 100
SP - 289
EP - 294
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 1
ER -