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 cost ...

-associated protein complex (DPC) of skeletal muscle cells. It is also a part of

BLOC-1 BLOC-1 or biogenesis of lysosome-related organelles complex 1 is a ubiquitously expressed multisubunit protein complex in a group of complexes that also includes BLOC-2 and BLOC-3. BLOC-1 is required for normal biogenesis of ...

, or

biogenesis of lysosome-related organelles complex 1 BLOC-1 or biogenesis of lysosome-related organelles complex 1 is a ubiquitously expressed multisubunit protein complex in a group of complexes that also includes BLOC-2 and BLOC-3. BLOC-1 is required for normal biogenesis of ...

. Dysbindin was discovered by the research group of

Derek Blake 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. He holds a doctorate (Doctor of Philosophy, D.Phil.) and a Bachelo ...

via

yeast two-hybrid Two-hybrid screening (originally known as yeast two-hybrid system or Y2H) is a molecular biology technique used to discover protein–protein interactions (PPIs) and protein–DNA interactions by testing for physical interactions (such as bind ...

screening for binding partners of α-dystrobrevin. In addition, dysbindin is found in

neural tissue Nervous tissue, also called neural tissue, is the main tissue (biology), tissue component of the nervous system. The nervous system regulates and controls body functions and activity. It consists of two parts: the central nervous system (CNS) com ...

of the

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...

, 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 p ...

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

, 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 Genetic may refer to: *Genetics, in biology, the science of genes, heredity, and the variation of organisms **Genetic, used as an adjective, refers to genes ***Genetic disorder, any disorder caused by a genetic mutation, whether inherited or de nov ...

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 A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...

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 platele ...

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 speci ...

, 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 Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...

with

SNAPAP SNARE-associated protein Snapin is a protein that in humans is encoded by the ''SNAPIN'' gene. Function SNAPAP is a component of the SNARE complex of proteins that is required for synaptic vesicle docking and fusion. SNAPAP is also a component ...

MUTED Protein Muted homolog is a protein that in humans is encoded by the ''MUTED'' gene. Function This gene encodes a component of BLOC-1 (biogenesis of lysosome-related organelles complex 1). Components of this complex are involved in the biogenes ...

and

PLDN Pallidin is a protein that in humans is encoded by the ''PLDN'' gene. Function The protein encoded by this gene may play a role in intracellular vesicle trafficking. It interacts with Syntaxin 13 which mediates intracellular membrane fusion. Se ...

References

External links

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