Dysbindin, short for dystrobrevin-binding protein 1, is a protein constituent of the

dystrophin Dystrophin is a rod-shaped cytoplasmic protein, and a vital part of a protein complex that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane. This complex is variously known as the cos ...

-associated protein complex (DPC) of

skeletal muscle Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of m ...

cells. It is also a part of BLOC-1, or biogenesis of lysosome-related organelles complex 1. Dysbindin was discovered by the research group of Derek Blake via yeast two-hybrid screening for binding partners of α-dystrobrevin. In addition, dysbindin is found in neural tissue of the

brain The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It consists of nervous tissue and is typically located in the head ( cephalization), usually near organs for special ...

, particularly in

axon An axon (from Greek ἄξων ''áxōn'', axis), or nerve fiber (or nerve fibre: see spelling differences), is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action ...

bundles and especially in certain axon terminals, notably mossy fiber synaptic terminals in the

cerebellum The cerebellum (Latin for "little brain") is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as or even larger. In humans, the cere ...

and

hippocampus The hippocampus (via Latin from Greek , ' seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, ...

. In humans, dysbindin is encoded by the ''DTNBP1''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

Clinical significance

Much interest in dysbindin has arisen through pedigree-based family-association studies of families with a history of

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wi ...

, 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 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 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

Hermansky–Pudlak syndrome Heřmanský–Pudlák syndrome (often written Hermansky–Pudlak syndrome or abbreviated HPS) is an extremely rare autosomal recessive disorder which results in oculocutaneous albinism (decreased pigmentation), bleeding problems due to a platelet ...

type 7. In

drosophila ''Drosophila'' () is a genus of flies, belonging to the family Drosophilidae, whose members are often called "small fruit flies" or (less frequently) pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many s ...

, dysbindin has been shown to be essential for

neural plasticity Neuroplasticity, also known as neural plasticity, or brain plasticity, is the ability of neural networks in the brain to change through growth and reorganization. It is when the brain is rewired to function in some way that differs from how it p ...

. *

Interactions

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

References

External links

GeneReviews/NCBI/NIH/UW entry on Hermansky–Pudlak syndrome
* {{Muscle tissue