Disrupted-In-Schizophrenia 1, a candidate gene for schizophrenia, participates in neurite outgrowth.
Disrupted-In-Schizophrenia 1 (DISC1) was identified as a novel gene disrupted by a (1;11)(q42.1;q14.3) translocation that segregated with schizophrenia in a Scottish family. Predicted DISC1 product has no significant homology to other known proteins. Here, we demonstrated the existence of DISC1 protein and identified fasciculation and elongation protein zeta-1 (FEZ1) as an interacting partner of DISC1 by a yeast two-hybrid study. FEZ1 and its nematode homolog are reported to represent a new protein family involved in axonal outgrowth and fasciculation. In cultured hippocampal neurons, DISC1 and FEZ1 colocalized in growth cones. Interactions of these proteins were associated with F-actin. In the course of neuronal differentiation of PC12 cells, upregulation of DISC1/FEZ1 interaction was observed as along with enhanced extension of neurites by overexpression of DISC1. The present study shows that DISC1 participates in neurite outgrowth through its interaction with FEZ1. Recent studies have provided reliable evidence that schizophrenia is a neurodevelopmental disorder. As there is a high level of DISC1 expression in developing rat brain, dysfunction of DISC1 may confer susceptibility to psychiatric illnesses through abnormal development of the nervous system.
Miyoshi
K
K
Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Japan.
Honda
A
A
Baba
K
K
Taniguchi
M
M
Oono
K
K
Fujita
T
T
Kuroda
S
S
Katayama
T
T
Tohyama
M
M
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000818:Animals; D002352:Carrier Proteins / Q000502:physiology*; D002460:Cell Line / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured / Q000378:metabolism / Q000648:ultrastructure; D003599:Cytoskeleton / Q000378:metabolism / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007668:Kidney; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D016501:Neurites / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D016716:PC12 Cells / Q000166:cytology; D011485:Protein Binding; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012559:Schizophrenia / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D020798:Two-Hybrid System Techniques
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C412476:DISC1 protein, human; D004268:DNA-Binding Proteins; C498795:Disc1 protein, rat; C528597:FEZ1 protein, human; C483740:Fez1 protein, rat; C118711:LZTS1 protein, human; D046911:Macromolecular Substances; D009419:Nerve Tissue Proteins; D011993:Recombinant Fusion Proteins; D025521:Tumor Suppressor Proteins