Disrupted in schizophrenia 1 (DISC1) is a candidate gene for susceptibility to schizophrenia. It was discovered through chromosomal analysis of a large Scottish family whose members exhibited schizophrenia and related psychiatric disorders. Through yeast two-hybrid screening, it was discovered that DISC1 interacts with many members of the centrosome and cytoskeletal system including MAP1A and Nudel. More recently, DISC1 has been found to regulate the transport of a complex containing Nudel, the lissencephaly-1 (LIS1) protein, and 14-3-3epsilon from neuronal cell bodies to the axons by the action of the microtubule-dependent directed motor protein kinesin-1, also known as KIF5A. Decreased expression of DISC1 in neurons caused an accelerated rate of neuronal integration, resulting in aberrant morphological development, suggesting that DISC1 plays a role in dendritic development and synapse formation. DISC1 has at least four known isoforms.
