Dysbindin
Encyclopedia
Dysbindin, short for dystrobrevin-binding protein 1, is a protein constituent of the dystrophin
-associated protein complex (DPC) of skeletal muscle
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
, particularly in axon
bundles and especially in certain axon terminals, notably mossy fiber synaptic terminals in the cerebellum
and hippocampus
. In humans, dysbindin is encoded by the DTNBP1 gene
.
-based family-association studies of families with a history of 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 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.
Probable 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
type 7.
In drosophila
, dysbindin has been shown to be essential for neural plasticity.
with SNAPAP
, MUTED
and PLDN
.
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 costamere or the dystrophin-associated protein complex...
-associated protein complex (DPC) of skeletal muscle
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
cells. It is also a part of BLOC-1, or biogenesis of lysosome-related organelles complex 1
Biogenesis of lysosome-related organelles complex 1
BLOC-1 or biogenesis of lysosome-related organelles complex 1 is a ubiquitously expressed multisubunit protein complex. BLOC-1 is required for normal biogenesis of specialized organelles of the endosomal-lysosomal system, such as melanosomes and platelet dense granules...
. Dysbindin was discovered by the research group of Derek Blake
Derek Blake
Dr Derek Blake was, until 2007, the Isobel Laing Post-Doctoral Fellow in Biomedical Sciences, and the Wellcome Trust Senior Fellow in Basic Biomedical Science, Oriel College, Oxford....
via yeast two-hybrid screening for binding partners of α-dystrobrevin. In addition, dysbindin is found in neural tissue of the brain
Brain
The brain is the center of the nervous system in all vertebrate and most invertebrate animals—only a few primitive invertebrates such as sponges, jellyfish, sea squirts and starfishes do not have one. It is located in the head, usually close to primary sensory apparatus such as vision, hearing,...
, particularly in axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
bundles and especially in certain axon terminals, notably mossy fiber synaptic terminals in the cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
and hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
. In humans, dysbindin is encoded by the DTNBP1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Clinical significance
Much interest in dysbindin has arisen through pedigreePedigree chart
A pedigree chart is a diagram that shows the occurrence and appearance or phenotypes of a particular gene or organism and its ancestors from one generation to the next, most commonly humans, show dogs, and race horses....
-based family-association studies of families with a history of schizophrenia
Schizophrenia
Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
, 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.
Probable 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
Hermansky-Pudlak syndrome
Hermansky–Pudlak syndrome is a rare autosomal recessive disorder which results in oculocutaneous albinism , bleeding problems due to a platelet abnormality , and storage of an abnormal fat-protein compound .There are eight classic forms of the disorder, based on the genetic mutation...
type 7.
In drosophila
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...
, dysbindin has been shown to be essential for neural plasticity.
Interactions
Dysbindin has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with SNAPAP
SNAPAP
SNARE-associated protein Snapin is a protein that in humans is encoded by the SNAPIN gene.-Interactions:SNAPAP has been shown to interact with SNAP-25, BLOC1S1, SNAP23, Dysbindin, TRPV1, PLDN, BLOC1S2 and RGS7.-Further reading:...
, MUTED
MUTED
Protein Muted homolog is a protein that in humans is encoded by the MUTED gene.-Interactions:MUTED has been shown to interact with BLOC1S2, Dysbindin and PLDN.-Further reading:...
and PLDN
PLDN
Pallidin is a protein that in humans is encoded by the PLDN gene.-Interactions:PLDN has been shown to interact with BLOC1S1, STX12, Dysbindin, CNO, BLOC1S2, MUTED and SNAPAP.-Further reading:...
.