DISC1 is a coordinator of intracellular trafficking to shape neuronal development and connectivity

Abstract

The long, asymmetric and specialised architecture of neuronal processes necessitates a properly regulated transport network of molecular motors and cytoskeletal tracks. This allows appropriate distribution of cargo for correct formation and activity of the synapse, and thus normal neuronal communication. This communication is impaired in psychiatric disease, and ongoing studies have proposed that Disrupted in schizophrenia 1 (DISC1) is an important genetic risk factor for these disorders. The mechanisms by which DISC1 dysfunction might increase propensity to psychiatric disease are not completely understood; however, an emerging theme is that DISC1 can function as a key regulator of neuronal intracellular trafficking. Transport of a wide range of potential cargoes – including mRNAs, neurotransmitter receptors, vesicles and mitochondria – can be modulated by DISC1, and therefore is susceptible to DISC1 dysfunction. This theme highlights the importance of understanding precisely how DISC1 can regulate intracellular trafficking, and suggests that a novel approach to the treatment of psychiatric disorders could be provided by targeting this protein and the trafficking machinery with which it interacts. (Figure presented.).