Intracellular Trafficking Defect May Underlie Schizophrenia

Schizophrenia has a strong genetic basis, although no single mutation causes the disease. Variations in the noncoding regions of DTNBP1, which encodes dysbindin, are associated with an increased risk of schizophrenia, and dysbindin expression is reduced in prefrontal cortex and hippocampus of schizophrenics. Dysbindin is part of a large endosomal protein complex called the “biogenesis of lysosome-related organelles complex 1” (BLOC-1), which is involved in trafficking protein-containing vesicles between intracellular compartments. To better understand dysbindin function, Gokhale et al. used mass spectrometry to identify proteins that interact with dysbindin in neuroblastoma cells. In addition to proteins previously shown to interact with dysbindin—including other BLOC-1 proteins—they identified 11 new interacting proteins. These included peroxiredoxins, proteins involved in vesicle trafficking to and within the Golgi apparatus, and several synapse-associated proteins. Interestingly, genes encoding eight of the interacting proteins are located in chromosomal regions in which allelic variations are associated with increased schizophrenia risk.