A change in the function of a protein in the cerebral cortex may contribute to the subtle neuronal defects observed in the brains of patients with schizophrenia, according to a paper in the December issue of Nature Cell Biology.
Such small changes in the brain's architecture are thought to be contributing factors in the development of the disease and here Akira Sawa and colleagues find that the DISC1 gene is part of a protein complex that is important for the normal movement of cells within the brain cortex during development.
The DISC1 gene is known to reside near the region of the chromosome which is broken, or 'translocated', in several schizophrenia patients from a particular Scottish pedigree. The gene binds to this complex of factors -- dynein, LIS1 and NUDEL -- and recruits them to the correct location in the cell. When the mutant form of DISC1 is present, as occurs in some schizophrenia patients, this complex no longer reaches the appropriate location. This complex is known to be important for normal neuronal growth in cell culture and for neuronal cells to migrate normally within the developing cortex. Sawa and colleagues now find that in the absence of DISC1, or when the mutant form of DISC1 is present, cell movement in the developing cerebral cortex is altered.
Together, these results suggest that DISC1 is important for normal formation of the cortex, through its effects on this complex, and that this function may be one reason neuronal development goes awry in a subset of schizophrenia patients.
Akira Sawa (Johns Hopkins University, Baltimore, MD, USA)
Abstract available online.
(C) Nature Cell Biology press release.
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