Disrupted-in-
schizophrenia 1 (DISC1) is a gene disrupted by a (1;11) (q42.1;q14.3) translocation that segregates with major
psychiatric disorders in a Scottish family. To investigate how DISC1 confers susceptibility to
psychiatric disorders, we previously identified
fasciculation and elongation
protein zeta-1 and
Kendrin as DISC1-interacting molecules in a yeast two-hybrid screen of a human brain
complementary DNA library. Here, we have further identified a novel DISC1-interacting
protein, termed DISC1-Binding Zinc-finger
protein (DBZ), which has a predicted C(2)H(2)-type zinc-finger motif and coiled-coil domains. DBZ was co-immunoprecipitated with DISC1 in lysates of PC12 cells and rat brain tissue. The domain of DISC1 interacting with DBZ was close to the translocation breakpoint in the DISC1 gene. DBZ
messenger RNA (
mRNA) was expressed in human brains, but not in peripheral tissues. In situ hybridization revealed high expression of DBZ
mRNA in the hippocampus, olfactory tubercle, cerebral cortex and striatum in rats. Because this pattern of localization was similar to that of the pituitary
adenylate cyclase (PAC(1)) receptor for
pituitary adenylate cyclase-activating polypeptide (
PACAP), which has recently been implicated in neuropsychological functions, we examined whether DISC1/DBZ interaction was involved in the
PACAP signaling pathway.
PACAP upregulated DISC1 expression and markedly reduced the association between DISC1 and DBZ in PC12 cells. A DISC1-binding domain of DBZ reduced the neurite length in PC12 cells after
PACAP stimulation and in primary cultured hippocampal neurons. The present results provide some new molecular insights into the mechanisms of neuronal development and neuropsychiatric disorders.