Much interest in dysbindin has arisen through pedigree-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.[6] 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.[7] In another work, damping down the DTNBP1 expression led to an increase in cell surface dopamine D2-receptor levels.[8]
^ abcGRCh38: Ensembl release 89: ENSG00000047579 - Ensembl, May 2017
^ abcGRCm38: Ensembl release 89: ENSMUSG00000057531 - Ensembl, May 2017
^"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ abcBenson; Newey, SE; Martin-Rendon, E; Hawkes, R; Blake, DJ; et al. (2001). "Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain". J Biol Chem. 276 (26): 24232–41. doi:10.1074/jbc.M010418200. PMID 11316798.
^Straub, R; Jiang, Y; MacLean, CJ; Ma, Y; Webb, BT; Myakishev, MV; Harris-Kerr, C; Wormley, B; et al. (2002). "Genetic Variation in the 6p22.3 Gene DTNBP1, the Human Ortholog of the Mouse Dysbindin Gene, Is Associated with Schizophrenia". Am J Hum Genet. 71 (2): 337–48. doi:10.1086/341750. PMC379166. PMID 12098102.
^Donohoe G, Morris DW, De Sanctis P, Magno E, Montesi JL, Garavan HP, Robertson IH, Javitt DC, Gill M, Corvin AP, Foxe JJ (2007). "Early Visual Processing Deficits in Dysbindin-Associated Schizophrenia". Biol Psychiatry. 63 (5): 484–9. doi:10.1016/j.biopsych.2007.07.022. hdl:2262/40654. PMID 17945199. S2CID 16722145.
^Iizuka Y, Sei Y, Weinberger DR, Straub RE (2007). "Evidence that the BLOC-1 protein dysbindin modulates dopamine D2 receptor internalization and signaling but not D1 internalization". J. Neurosci. 27 (45): 12390–5. doi:10.1523/JNEUROSCI.1689-07.2007. PMC6673263. PMID 17989303.
^Li W, Zhang Q, Oiso N, Novak EK, Gautam R, O'Brien EP, Tinsley CL, Blake DJ, Spritz RA, Copeland NG, Jenkins NA, Amato D, Roe BA, Starcevic M, Dell'Angelica EC, Elliott RW, Mishra V, Kingsmore SF, Paylor RE, Swank RT (2003). "Hermansky–Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1)". Nat. Genet. 35 (1): 84–9. doi:10.1038/ng1229. PMC2860733. PMID 12923531.
"Schizophrenia gene's role may be broader, more potent, than thought". Phys.org. November 19, 2009.
^ abcStarcevic M, Dell'Angelica EC (July 2004). "Identification of snapin and three novel proteins (BLOS1, BLOS2, and BLOS3/reduced pigmentation) as subunits of biogenesis of lysosome-related organelles complex-1 (BLOC-1)". J. Biol. Chem. 279 (27): 28393–401. doi:10.1074/jbc.M402513200. PMID 15102850.
External linksedit
GeneReviews/NCBI/NIH/UW entry on Hermansky–Pudlak syndrome
dysbindin, short, dystrobrevin, binding, protein, protein, constituent, dystrophin, associated, protein, complex, skeletal, muscle, cells, also, part, bloc, biogenesis, lysosome, related, organelles, complex, discovered, research, group, derek, blake, yeast, h. 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 a dystrobrevin 5 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 5 In humans dysbindin is encoded by the DTNBP1 gene 5 DTNBP1IdentifiersAliasesDTNBP1 BLOC1S8 DBND HPS7 My031 SDY dystrobrevin binding protein 1External IDsOMIM 607145 MGI 2137586 HomoloGene 12037 GeneCards DTNBP1Gene location Human Chr Chromosome 6 human 1 Band6p22 3Start15 522 807 bp 1 End15 663 058 bp 1 Gene location Mouse Chr Chromosome 13 mouse 2 Band13 A5 13 21 73 cMStart45 075 551 bp 2 End45 155 623 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed innucleus accumbensputameninternal globus palliduscaudate nucleushypothalamusamygdalacingulate gyrussubstantia nigraprefrontal cortexBrodmann area 9Top expressed ininterventricular septumspermatocyteyolk sacsuperior frontal gyrusbrown adipose tissuevisual cortexmyocardium of ventriclesoleus musclewhite adipose tissueskeletal muscle tissueMore reference expression dataBioGPSn aGene ontologyMolecular functionprotein bindingCellular componentcytoplasm cytosol endosome postsynaptic membrane endoplasmic reticulum membrane membrane postsynaptic density growth cone BLOC 1 complex plasma membrane dendritic spine synapse synaptic vesicle membrane melanosome membrane axon cell junction endoplasmic reticulum sarcoplasm neuron projection sarcolemma endosome membrane cytoplasmic vesicle membrane cytoplasmic vesicle nucleus axon cytoplasm microtubule cytoskeleton midbody asymmetric synapse Schaffer collateral CA1 synapse hippocampal mossy fiber to CA3 synapse glutamatergic synapseBiological processactin cytoskeleton reorganization regulation of dopamine secretion neuron projection morphogenesis platelet dense granule organization response to stimulus regulation of dopamine receptor signaling pathway positive regulation of neurotransmitter secretion blood coagulation organelle organization anterograde axonal transport melanosome organization positive regulation of gene expression anterograde synaptic vesicle transport neuron projection development regulation of JUN kinase activity negative regulation of protein serine threonine kinase activity dendrite morphogenesis negative regulation of protein binding regulation of synaptic vesicle exocytosisSources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez8406294245EnsemblENSG00000047579ENSMUSG00000057531UniProtQ96EV8Q91WZ8RefSeq mRNA NM 001271667NM 001271668NM 001271669NM 032122NM 183040NM 025772RefSeq protein NP 001258596NP 001258597NP 001258598NP 115498NP 898861NP 080048Location UCSC Chr 6 15 52 15 66 MbChr 13 45 08 45 16 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Clinical significance 2 Interactions 3 References 4 External linksClinical significance editMuch interest in dysbindin has arisen through pedigree 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 6 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 7 In another work damping down the DTNBP1 expression led to an increase in cell surface dopamine D2 receptor levels 8 Mutation in the DTNBP1 gene was also shown to cause Hermansky Pudlak syndrome type 7 9 In drosophila dysbindin has been shown to be essential for neural plasticity 10 Interactions editDysbindin has been shown to interact with SNAPAP 11 MUTED 11 and PLDN 11 References edit a b c GRCh38 Ensembl release 89 ENSG00000047579 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000057531 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b c Benson Newey SE Martin Rendon E Hawkes R Blake DJ et al 2001 Dysbindin a novel coiled coil containing protein that interacts with the dystrobrevins in muscle and brain J Biol Chem 276 26 24232 41 doi 10 1074 jbc M010418200 PMID 11316798 Straub R Jiang Y MacLean CJ Ma Y Webb BT Myakishev MV Harris Kerr C Wormley B et al 2002 Genetic Variation in the 6p22 3 Gene DTNBP1 the Human Ortholog of the Mouse Dysbindin Gene Is Associated with Schizophrenia Am J Hum Genet 71 2 337 48 doi 10 1086 341750 PMC 379166 PMID 12098102 Donohoe G Morris DW De Sanctis P Magno E Montesi JL Garavan HP Robertson IH Javitt DC Gill M Corvin AP Foxe JJ 2007 Early Visual Processing Deficits in Dysbindin Associated Schizophrenia Biol Psychiatry 63 5 484 9 doi 10 1016 j biopsych 2007 07 022 hdl 2262 40654 PMID 17945199 S2CID 16722145 Iizuka Y Sei Y Weinberger DR Straub RE 2007 Evidence that the BLOC 1 protein dysbindin modulates dopamine D2 receptor internalization and signaling but not D1 internalization J Neurosci 27 45 12390 5 doi 10 1523 JNEUROSCI 1689 07 2007 PMC 6673263 PMID 17989303 Li W Zhang Q Oiso N Novak EK Gautam R O Brien EP Tinsley CL Blake DJ Spritz RA Copeland NG Jenkins NA Amato D Roe BA Starcevic M Dell Angelica EC Elliott RW Mishra V Kingsmore SF Paylor RE Swank RT 2003 Hermansky Pudlak syndrome type 7 HPS 7 results from mutant dysbindin a member of the biogenesis of lysosome related organelles complex 1 BLOC 1 Nat Genet 35 1 84 9 doi 10 1038 ng1229 PMC 2860733 PMID 12923531 Dickman DK Davis GW November 2009 The Schizophrenia Susceptibility Gene Dysbindin Controls Synaptic Homeostasis Science 326 5956 1127 30 Bibcode 2009Sci 326 1127D doi 10 1126 science 1179685 PMC 3063306 PMID 19965435 Schizophrenia gene s role may be broader more potent than thought Phys org November 19 2009 a b c Starcevic M Dell Angelica EC July 2004 Identification of snapin and three novel proteins BLOS1 BLOS2 and BLOS3 reduced pigmentation as subunits of biogenesis of lysosome related organelles complex 1 BLOC 1 J Biol Chem 279 27 28393 401 doi 10 1074 jbc M402513200 PMID 15102850 External links editGeneReviews NCBI NIH UW entry on Hermansky Pudlak syndrome Dysbindin at the U S National Library of Medicine Medical Subject Headings MeSH Retrieved from https en wikipedia org w index php title Dysbindin amp oldid 1126323390, wikipedia, wiki, book, books, library,
