DISC1 is a promising risk factor for schizophrenia and mood disorders. DISC1 may also be involved in cognitive dysfunction associated with aging. Recent studies have suggested that DISC1 is multifunctional, with various isoforms (indeed, there are many more kinds of DISC1 isoforms than already published). An outstanding paper by Camargo, Brandon, and colleagues approached this fascinating, but complicated, molecule with a very unique approach. The authors conducted several sets of yeast two-hybrid screening with DISC1 and related proteins as baits, analyzed the experimental data with sophisticated bioinformatic methods, and generated a “DISC1 interactome map.”

The map is consistent with previous experimental reports. More importantly, it suggests a role for DISC1 in synaptic maturation and regulation. DISC1 and dysbindin, another promising risk factor for schizophrenia, share common protein-protein interactions, suggesting that these two risk factors may be in the same disease pathway. At the Society for Neuroscience meeting held in Atlanta last week, several groups presented a role for dysbindin at not only presynaptic but also postsynaptic sites. As Kirkpatrick and colleagues reported (Kirkpatrick et al., 2006; see SRF related news story), a pool of DISC1 is localized in the postsynaptic regions in matured neurons. Taken together, it would be very interesting to explore how DISC1 and dysbindin may crosstalk at the postsynaptic sites. In order to understand the “disease pathway(s),” it is becoming more and more important to organize functions of the disease risk factors in biological contexts. Therefore, the approach that Camargo and Brandon took in this paper may have broader application to schizophrenia research.

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