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Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth.

http://www.ncbi.nlm.nih.gov/pubmed/12506198

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.

Pubmed ID: 12506198 RIS Download

Mesh terms: Animals | Cloning, Molecular | Cysteine Endopeptidases | DNA Primers | Humans | Nerve Tissue Proteins | Neurites | Protein Binding | Rats | Recombinant Proteins | Reverse Transcriptase Polymerase Chain Reaction | Sequence Deletion | Serine Endopeptidases | Subcellular Fractions

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Associated grants

  • Agency: NIDA NIH HHS, Id: DA-00074
  • Agency: NINDS NIH HHS, Id: NS-34172

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