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Dysbindin

DTNBP1
Identifiers
AliasesDTNBP1, BLOC1S8, DBND, HPS7, My031, SDY, dystrobrevin binding protein 1
External IDsOMIM: 607145; MGI: 2137586; HomoloGene: 12037; GeneCards: DTNBP1; OMA:DTNBP1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

84062

94245

Ensembl

ENSG00000047579

ENSMUSG00000057531

UniProt

Q96EV8

Q91WZ8

RefSeq (mRNA)

NM_001271667
NM_001271668
NM_001271669
NM_032122
NM_183040

NM_025772

RefSeq (protein)

NP_001258596
NP_001258597
NP_001258598
NP_115498
NP_898861

NP_080048

Location (UCSC)Chr 6: 15.52 – 15.66 MbChr 13: 45.08 – 45.16 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[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]

Clinical significance

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]

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

Dysbindin has been shown to interact with SNAPAP,[11] MUTED[11] and PLDN.[11]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000047579 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000057531 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ 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.
  6. ^ 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.
  7. ^ 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.
  8. ^ 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.
  9. ^ 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.
  10. ^ 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.
  11. ^ 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.
Quelle: https://en.wikipedia.org/wiki/Dysbindin