Dysbindin

Dysbindin, short for dystrobrevin-binding protein 1, is a protein constituent of the is_associated_with::dystrophin-associated protein complex (DPC) of is_associated_with::skeletal muscle cells. It is also a part of is_associated_with::BLOC-1, or is_associated_with::biogenesis of lysosome-related organelles complex 1. Dysbindin was discovered by the research group of is_associated_with::Derek Blake via is_associated_with::yeast two-hybrid screening for binding partners of α-dystrobrevin. In addition, dysbindin is found in is_associated_with::neural tissue of the is_associated_with::brain, particularly in is_associated_with::axon bundles and especially in certain axon terminals, notably mossy fiber is_associated_with::synaptic terminals in the is_associated_with::cerebellum and is_associated_with::hippocampus. In humans, dysbindin is encoded by the DTNBP1 is_associated_with::gene.

Clinical significance
Much interest in dysbindin has arisen through pedigree-based family-association studies of families with a history of is_associated_with::schizophrenia, where a strong association was found between expression of a particular dysbindin allele and a clinical expression of schizophrenia. However, the genetic link between dysbindin and schizophrenia has not been established in all the case control samples tested and this implies that there are different genetic subtypes of schizophrenia with different disease allele frequencies in different populations. This phenomenon is called is_associated_with::genetic locus heterogeneity and is typical of all common disorders with a strong genetic component. A further complication is that it is highly likely that there are several or many different mutations within the dysbindin gene that are responsible for schizophrenia. This complexity is called is_associated_with::disease allele heterogeneity and is a further reason that genetic associations are found with different markers in the dysbindin gene when different samples are studied.

Genetically caused dysbindin-related mechanisms causing brain dysfunction are not fully known, but in one study, schizophrenic patients carrying the high-risk haplotype demonstrated visual processing deficits. In another work, damping down the DTNBP1 expression led to an increase in cell surface dopamine D2-receptor levels.

Mutation in the DTNBP1 gene was also shown to cause is_associated_with::Hermansky-Pudlak syndrome type 7.

In is_associated_with::drosophila, dysbindin has been shown to be essential for is_associated_with::neural plasticity.

Interactions
Dysbindin has been shown to interact with is_associated_with::SNAPAP, is_associated_with::MUTED and is_associated_with::PLDN.