title: Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth.
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.
authors.affiliation: Division of Neurobiology and Department of Psychiatry, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ozeki
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tomoda
authors.forename: John
authors.initials: J
authors.lastname: Kleiderlein
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kamiya
authors.forename: Lyuda
authors.initials: L
authors.lastname: Bord
authors.forename: Kumiko
authors.initials: K
authors.lastname: Fujii
authors.forename: Masako
authors.initials: M
authors.lastname: Okawa
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamada
authors.forename: Mary E
authors.initials: ME
authors.lastname: Hatten
authors.forename: Solomon H
authors.initials: SH
authors.lastname: Snyder
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ross
authors.forename: Akira
authors.initials: A
authors.lastname: Sawa
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D003546:Cysteine Endopeptidases; D017931:DNA Primers; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D016501:Neurites / Q000502:physiology*; D011485:Protein Binding; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D012697:Serine Endopeptidases / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: C412476:DISC1 protein, human; D017931:DNA Primers; C498795:Disc1 protein, rat; D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D012697:Serine Endopeptidases; D003546:Cysteine Endopeptidases; C516549:Ndel1 protein, rat