Affinage

Showing DTNBP1 — BLOC1S8 is a alias.

DTNBP1

Dysbindin · UniProt Q96EV8

Length
351 aa
Mass
39.5 kDa
Annotated
2026-06-09
100 papers in source corpus 40 papers cited in narrative 41 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

Dysbindin-1 (DTNBP1) is a coiled-coil protein that functions as a core, stably assembled subunit of the octameric BLOC-1 complex, coordinating endosomal cargo sorting and presynaptic vesicle biology in neurons (PMID:16448387, PMID:21998198). Originally identified as a direct binding partner of alpha- and beta-dystrobrevin in muscle and brain (PMID:11316798), its dystrobrevin-binding coiled-coil region is in fact occupied within assembled BLOC-1 by pallidin, snapin, and muted, so the physiological pool is BLOC-1-bound rather than dystrobrevin-bound (PMID:16448387). Acting with the AP-3 complex through the AP-3 mu subunit, BLOC-1/dysbindin traffics cargo such as PI4KIIalpha from neuronal cell bodies to nerve terminals (PMID:19428785, PMID:21998198), and directs internalized D2 dopamine and delta-opioid receptors toward lysosomal degradation via interactions with GASP-1 and HRS, so that dysbindin loss elevates surface D2 receptor and augments downstream signaling (PMID:17989303, PMID:20174469). Presynaptically, dysbindin sets dense-core and synaptic vesicle size, the readily releasable pool, release probability, and exo/endocytosis kinetics, thereby controlling glutamate and BDNF release (PMID:18504299, PMID:23473812, PMID:26386481); in Drosophila it is required for retrograde homeostatic modulation of release acting together with NSF and the Arp2/3 actin machinery (PMID:19965435, PMID:27927957, PMID:25972187). Postsynaptically it limits surface NR2A NMDA receptor expression and constrains hippocampal LTP (PMID:19955431), and it shapes dendritic spine morphogenesis through a ternary complex with WAVE2 and Abi-1 (PMID:20531346, PMID:25297099). Dysbindin also undergoes CRM1-dependent nucleocytoplasmic shuttling that regulates synapsin I expression (PMID:20921223) and is degraded by the E3 ubiquitin ligase TRIM32, an activity antagonized by TRIM24 (PMID:19349376, PMID:28465353).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2001 High

    Established the molecular identity of dysbindin as a coiled-coil protein with a defined binding partner, anchoring it to the dystrophin/dystrobrevin protein complex in muscle and to synaptic terminals in brain.

    Evidence Yeast two-hybrid, reciprocal co-IP, and immunolocalization in muscle and brain

    PMID:11316798

    Open questions at the time
    • Did not establish whether dystrobrevin binding occurs in the physiological assembled state
    • No functional role defined
  2. 2006 High

    Resolved the apparent dystrobrevin association by showing dysbindin is a stable BLOC-1 subunit whose coiled-coil region is occupied by pallidin, snapin, and muted, reframing its physiological context as an endosomal sorting complex.

    Evidence Yeast two-hybrid, recombinant binding assays, and endogenous co-IP from brain and muscle (plus snapin interaction and ultrastructural localization to synaptic vesicles)

    PMID:16448387 PMID:16980328

    Open questions at the time
    • BLOC-1 cargo repertoire not yet defined
    • Functional consequence of snapin binding not yet established
  3. 2004 Medium

    First functional role in neurons: bidirectional manipulation showed dysbindin promotes presynaptic protein expression and glutamate release and supports neuronal survival via PI3K-Akt signaling.

    Evidence Overexpression/siRNA in primary cortical neurons with glutamate ELISA, pAkt Western, and LY294002 epistasis

    PMID:15345706

    Open questions at the time
    • Mechanism linking dysbindin to Akt activation unresolved
    • Single lab, overexpression-based
  4. 2008 High

    Genetic-null analysis defined dysbindin as a regulator of vesicle biogenesis and exocytosis, controlling dense-core vesicle size, release probability, and the readily releasable pool.

    Evidence Amperometry, patch clamp, and EM in sandy (sdy) dysbindin-null mice

    PMID:18504299

    Open questions at the time
    • Molecular link from BLOC-1 to vesicle biophysics not mapped
    • Did not distinguish dense-core from clear-vesicle pathways mechanistically
  5. 2009 High

    Connected dysbindin/BLOC-1 to GPCR trafficking and dopaminergic signaling, showing it limits surface D2 receptor levels and shapes interneuron and pyramidal excitability and working memory.

    Evidence siRNA and knockout-mouse imaging, fractionation, receptor trafficking assays, and electrophysiology (D2 surface levels, pCREB readouts)

    PMID:17989303 PMID:19641486 PMID:19887632

    Open questions at the time
    • Whether D2 effect is via altered recycling vs degradation initially ambiguous
    • Selectivity for D2 over D1 mechanism not fully explained
  6. 2009 High

    Identified the postsynaptic NMDA receptor arm and presynaptic interactome, showing dysbindin selectively restrains surface NR2A to constrain LTP and binds Munc18-1 and AP-3 mu at terminals.

    Evidence Imaging/biotinylation and LTP recordings in null mice; proteomics, co-IP, and in vitro binding for Munc18-1 and AP-3

    PMID:19428785 PMID:19573021 PMID:19955431

    Open questions at the time
    • Mechanism of NR2A-selective regulation undefined
    • How vesicle partners and trafficking integrate not resolved
  7. 2009 High

    Defined a degradation control point: TRIM32 ubiquitinates dysbindin to drive its turnover, with LGMD2H/STM disease alleles impairing this ligase activity.

    Evidence Yeast two-hybrid, in vitro/cell ubiquitination assays, siRNA, and disease-allele mutagenesis (D487N, R394H)

    PMID:19349376

    Open questions at the time
    • Physiological signals controlling TRIM32-dysbindin turnover unknown
    • In vivo consequence of altered turnover not tested
  8. 2011 High

    Mechanistically unified dysbindin's trafficking role by showing BLOC-1/AP-3 transports cargo (PI4KIIalpha) from neuronal cell bodies to neurites, defining the somatodendritic-to-terminal sorting pathway.

    Evidence Co-purification, AP-3 and BLOC-1 knockout mice, sorting-motif mutagenesis, and imaging in neurons/PC12 cells

    PMID:21998198

    Open questions at the time
    • Full cargo set transported by this route not enumerated
    • Link between cargo mis-sorting and synaptic phenotypes incompletely traced
  9. 2011 Medium

    Expanded dysbindin beyond trafficking into cytoskeletal, nuclear, and transcriptional roles, including WAVE2/Abi-1-dependent spine morphogenesis, CRM1-dependent shuttling regulating synapsin I, and necdin/p53-dependent neurite outgrowth.

    Evidence Co-IP/Y2H, RNAi morphology, leptomycin B/NES mutagenesis, and p53 reporter/rescue assays in neurons and sdy mice

    PMID:20531346 PMID:20921223 PMID:21502952

    Open questions at the time
    • Relationship between nuclear shuttling and BLOC-1 function unclear
    • Single-lab findings for several non-canonical roles
  10. 2011 Medium

    Linked dysbindin to disease-relevant protein interactions and Drosophila cell-type dissection, including direct DISC1 binding/co-aggregation in patient brain and distinct neuronal vs glial roles controlling glutamatergic transmission and dopamine metabolism.

    Evidence Cell-free recombinant binding/domain mapping and postmortem brain co-IP; cell-type-specific RNAi with electrophysiology and behavior in Drosophila

    PMID:21531389 PMID:22049342

    Open questions at the time
    • Functional consequence of DISC1 co-aggregation in vivo not established
    • Conservation of glial mechanism to mammals untested
  11. 2015 High

    Defined effector machinery for homeostatic plasticity and actin-dependent endosomal function, showing dysbindin/BLOC-1 controls NSF and Arp2/3 levels and copper-stress resistance, with NSF or dysbindin rescuing homeostatic plasticity in Drosophila.

    Evidence Proteome-wide screens, co-IP, actin dynamics assays, and Drosophila genetic rescue/interaction electrophysiology

    PMID:25972187 PMID:26199316 PMID:27927957

    Open questions at the time
    • Direct vs indirect regulation of NSF/Arp2/3 abundance unresolved
    • Mammalian relevance of copper phenotype incompletely defined
  12. 2015 High

    Identified a transsynaptic signaling output: dysbindin controls BDNF exocytosis from excitatory neurons, which in turn sets the number of inhibitory synapses, rescuable by exogenous BDNF.

    Evidence TIRF live-cell BDNF imaging, whole-cell recordings, IHC, and BDNF rescue in cortical neurons and slices

    PMID:26386481

    Open questions at the time
    • Mechanism coupling dysbindin to BDNF vesicle exocytosis specifically not detailed
    • In vivo circuit-level validation limited
  13. 2017 Medium

    Established antagonistic control of dysbindin stability beyond muscle, with TRIM24 shielding dysbindin from TRIM32-mediated degradation to tune RhoA-SRF-driven cardiomyocyte hypertrophy.

    Evidence Yeast two-hybrid, co-IP, TRIM24/TRIM32 manipulation Westerns, and SRF reporter/hypertrophy assays in cardiomyocytes

    PMID:24385487 PMID:28465353

    Open questions at the time
    • Whether TRIM24/TRIM32 balance regulates neuronal dysbindin untested
    • Upstream regulation of the TRIM switch unknown
  14. 2018 Medium

    Refined the dopaminergic mechanism and clinical relevance, showing dysbindin expression controls vesicle pools recruited during homeostatic plasticity and the D2 short/long isoform balance shaping prefrontal D2 function and antipsychotic response.

    Evidence Drosophila NMJ electrophysiology with proteasome inhibition/EGTA assays; postmortem human brain and genetically modified mouse D2 isoform analysis

    PMID:29348419 PMID:29891954

    Open questions at the time
    • Causal chain from dysbindin level to D2 isoform ratio not fully mapped
    • Single-lab human-mouse convergence

Open questions

Synthesis pass · forward-looking unresolved questions
  • How dysbindin's multiple roles—BLOC-1 endosomal sorting, presynaptic vesicle pool control, postsynaptic receptor surface regulation, nuclear shuttling, and proteostatic turnover—are coordinated within a single neuron and selectively engaged across cell types remains unresolved.
  • No integrated model linking BLOC-1 trafficking to the non-canonical nuclear/transcriptional roles
  • Structural basis of cargo selection by dysbindin/BLOC-1 undefined
  • In vivo hierarchy of pre- vs post-synaptic dysbindin functions unestablished

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0060090 molecular adaptor activity 3 GO:0005198 structural molecule activity 1
Localization
GO:0005768 endosome 3 GO:0005886 plasma membrane 3 GO:0031410 cytoplasmic vesicle 3 GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 3 R-HSA-5653656 Vesicle-mediated transport 3 R-HSA-392499 Metabolism of proteins 2 R-HSA-9609507 Protein localization 1
Partners
ABI1AP3M1MUTEDPLDNSNAPINSTXBP1TRIM32WASF2
Complex memberships
BLOC-1

Evidence

Reading pass · 41 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Dysbindin (DTNBP1) is a novel coiled-coil-containing protein that binds directly to alpha- and beta-dystrobrevin in muscle and brain, is co-immunoprecipitated with dystrophin and alpha-dystrobrevin (indicating DPC association in muscle), co-localizes with alpha-dystrobrevin at the sarcolemma, and is found in axon bundles and mossy fiber synaptic terminals in brain. Yeast two-hybrid screen, co-immunoprecipitation, immunolocalization The Journal of biological chemistry High 11316798
2003 Dysbindin binds to myospryn, a novel 413-kDa muscle protein, and the two proteins co-immunoprecipitate from muscle extracts and are extensively co-localized, demonstrating a tissue-specific binding partner for dysbindin in muscle. Yeast two-hybrid screen, co-immunoprecipitation, co-localization immunofluorescence The Journal of biological chemistry Medium 14688250
2004 Overexpression of dysbindin in primary cortical neurons increases expression of presynaptic proteins SNAP25 and synapsin I and enhances extracellular glutamate release; siRNA knockdown reduces both presynaptic protein expression and glutamate release, indicating dysbindin regulates exocytotic glutamate release via upregulation of presynaptic machinery. Neuronal overexpression and siRNA knockdown, ELISA glutamate measurement, Western blotting Human molecular genetics Medium 15345706
2004 Dysbindin overexpression increases Akt phosphorylation and protects cortical neurons against serum deprivation-induced death via PI3-kinase–Akt signaling; these effects are blocked by the PI3-kinase inhibitor LY294002, and siRNA knockdown of dysbindin diminishes Akt phosphorylation and facilitates neuronal death. Neuronal overexpression and siRNA knockdown, pharmacological inhibition (LY294002), Western blotting for pAkt, cell viability assays Human molecular genetics Medium 15345706
2006 Dysbindin-1 binds snapin in vitro and in brain; both proteins are concentrated in synaptic vesicle membrane fractions and less so in postsynaptic densities, with immunoelectron microscopy showing dysbindin-1 in synaptic vesicles of axospinous terminals and in postsynaptic densities and microtubules of hippocampal neurons. In vitro binding assay, tissue fractionation, co-immunoprecipitation, immunoelectron microscopy Human molecular genetics High 16980328
2006 Dysbindin is a stable subunit of the BLOC-1 complex; within BLOC-1 its dystrobrevin-binding region (69-residue coiled-coil) is occupied by interactions with pallidin, snapin, and muted subunits. Recombinant dystrobrevin coiled-coil fragments fail to pull down endogenous BLOC-1 from brain or muscle, and immunoprecipitation of endogenous dysbindin from brain or muscle co-precipitates pallidin but not dystrobrevin isoforms, indicating that BLOC-1-assembled dysbindin is not a physiological dystrobrevin-binding partner. Yeast two-hybrid, recombinant protein binding assays, co-immunoprecipitation of endogenous proteins from brain and muscle The Biochemical journal High 16448387
2007 DTNBP1 siRNA knockdown decreases dysbindin protein, increases cell-surface D2 receptor (DRD2) levels, and blocks dopamine-induced DRD2 internalization in SH-SY5Y cells and rat primary cortical neurons; MUTED siRNA produces similar effects; DRD1 levels and internalization are unaffected. Enhanced DRD2 surface levels lead to increased quinpirole-induced reduction of CREB phosphorylation, demonstrating augmented intracellular signaling. siRNA knockdown, flow cytometry / immunofluorescence for surface receptor quantification, Western blotting for pCREB The Journal of neuroscience High 17989303
2008 Loss of dysbindin in sandy (sdy) mice causes larger dense-core vesicle size, slower quantal release kinetics, lower release probability, and a smaller readily releasable vesicle pool in neuroendocrine cells and hippocampal synapses, indicating dysbindin regulates exocytosis and vesicle biogenesis. Amperometry, whole-cell patch clamp, electron microscopy in dysbindin-null (sdy) mice The Journal of cell biology High 18504299
2008 Dysbindin-null (sdy) mice have reduced dopamine (but not glutamate) levels in cerebral cortex, hippocampus, and hypothalamus, linking dysbindin deficiency to reduced forebrain dopaminergic transmission. Neurochemical quantification (HPLC) in dysbindin-null (sdy) mice brain regions Biochemical and biophysical research communications Medium 18555792
2008 In dysbindin-null (sdy) mice, steady-state snapin protein is reduced in hippocampus; a 30-residue peptide (amino acids 90–119) of dysbindin mediates the interaction with snapin, and its loss destabilizes snapin leading to abnormal neurotransmission. Western blotting in sdy mice, peptide binding/interaction mapping Schizophrenia research Medium 18774265
2009 TRIM32 is an E3 ubiquitin ligase that binds dysbindin via yeast two-hybrid, ubiquitinates it to augment its degradation, and siRNA knockdown of TRIM32 elevates dysbindin levels. LGMD2H/STM-associated mutations D487N and R394H impair ubiquitin ligase activity toward dysbindin while retaining dysbindin-binding ability; D487N can bind dysbindin and its E2 but is defective in monoubiquitination. Yeast two-hybrid, in vitro/cell-based ubiquitination assays, siRNA knockdown, Western blotting, co-immunoprecipitation Human molecular genetics High 19349376
2009 Drosophila dysbindin is required presynaptically for retrograde homeostatic modulation of neurotransmission in a dose-dependent manner, functioning downstream of or independently of calcium influx, as established by an electrophysiology-based forward genetic screen at the neuromuscular junction. Forward genetic screen, electrophysiology (mEJP, EJP recording), genetic epistasis with calcium channel mutations Science High 19965435
2009 In dysbindin-knockout (dys−/−) mice, D2 receptor (but not D1) surface expression is robustly increased due to enhanced recycling and insertion rather than reduced endocytosis; fast-spiking GABAergic interneurons in PFC and striatum show decreased excitability; inhibitory input to PFC pyramidal neurons is decreased; and D2 agonist produces a more pronounced increase in interneuron firing in dys−/− compared to wild-type. Cell imaging, biochemical fractionation, whole-cell electrophysiology, receptor trafficking assays in genetic knockout mice Proceedings of the National Academy of Sciences of the United States of America High 19887632
2009 Dysbindin controls hippocampal LTP by selectively reducing surface expression of NR2A (but not NR2B) NMDA receptor subunits; dysbindin-null hippocampal neurons show increased surface NR2A by imaging and biotinylation, increased NR2A-mediated synaptic currents, and enhanced LTP without changes in basal transmission, AMPA receptor currents, or LTD. Fluorescence imaging, surface biotinylation, whole-cell electrophysiology (patch clamp), LTP/LTD field recordings in hippocampal slices from genetic null mice Proceedings of the National Academy of Sciences of the United States of America High 19955431
2009 Dysbindin-null mice show reduced paired-pulse facilitation and reduced evoked and miniature excitatory post-synaptic currents in deep-layer PFC pyramidal neurons, indicating a presynaptic deficit in glutamatergic transmission that is associated with impaired spatial working memory. Whole-cell patch clamp recordings in PFC slices, behavioral spatial working memory task in genetic null mice Neuropsychopharmacology Medium 19641486
2009 Direct interaction between dysbindin and the AP-3 complex is mediated through the mu subunit of AP-3; dysbindin partially co-localizes with AP-3 in hippocampal CA1/CA3 and at presynaptic terminals and growth cones; dysbindin suppression reduces presynaptic protein expression and glutamate release. Co-immunoprecipitation, in vitro binding assay, immunofluorescence co-localization, siRNA knockdown with glutamate release assay Neurochemistry international Medium 19428785
2009 Proteomics of dysbindin-interacting proteins from rat brain identifies Munc18-1 as a binding partner; Munc18-1 co-immunoprecipitates with dysbindin from rat brain lysate, interacts directly in vitro, and co-localizes with dysbindin at presynaptic terminals in cultured hippocampal neurons. Affinity chromatography, MALDI-TOF/LC-MS/MS proteomics, co-immunoprecipitation, in vitro binding assay, immunofluorescence Journal of neurochemistry Medium 19573021
2009 Cytosolic immunoprecipitation/mass spectrometry of dysbindin identifies novel interactions with members of the exocyst, dynactin, and chaperonin containing T-complex protein (CCT) complexes, in addition to confirming all BLOC-1 and AP-3 subunit interactions. Co-immunoprecipitation, mass spectrometry, Western blot validation in mammalian cells Journal of neurochemistry Medium 20236384
2010 Dysbindin knockdown in HEK293 and HeLa cells specifically reduces post-endocytic lysosomal trafficking of internalized D2 receptors (and delta opioid receptors) without affecting receptor endocytosis; dysbindin co-immunoprecipitates with GASP-1 and HRS (ESCRT component), suggesting it promotes lysosomal sorting of specific GPCRs. RNA interference, immunochemistry, biochemical trafficking assays, co-immunoprecipitation in non-neuronal cells PloS one Medium 20174469
2010 Dysbindin-1 and WAVE2 and Abi-1 form a ternary complex; dysbindin-1 promotes the binding of WAVE2 to Abi-1; siRNA knockdown of dysbindin-1 in hippocampal neurons leads to elongated immature dendritic protrusions, indicating a role in dendritic spine morphogenesis. Co-immunoprecipitation, yeast two-hybrid, RNAi knockdown with morphological analysis of dendritic spines Molecular psychiatry Medium 20531346
2010 Dysbindin-1 is a nucleocytoplasmic shuttling protein with a functional nuclear export signal; inhibition of CRM1/exportin-1-mediated nuclear export (leptomycin B) causes nuclear accumulation of dysbindin-1; nucleocytoplasmic shuttling regulates synapsin I expression; dysbindin-1-null (sdy) mice have reduced synapsin I protein and mRNA. Leptomycin B treatment, nuclear export signal mutagenesis, subcellular fractionation, Western blotting in sandy mice The Journal of biological chemistry Medium 20921223
2010 Dysbindin deficiency in dys−/− mice is associated with reduced NMDA-evoked currents in PFC pyramidal neurons and decreased NR1 subunit expression; the degree of NR1 expression correlates with spatial working memory performance. Whole-cell recordings in PFC slices, quantitative RT-PCR for NR1, behavioral spatial working memory testing in genetic null mice Biological psychiatry Medium 21035792
2010 Dysbindin-1 disruption in dys−/− mice reduces CaMKII and CaMKKβ expression in mPFC; chronic D2 agonist treatment reproduces these protein expression changes; dys−/− pyramidal neurons are hyperexcitable at baseline but hypoexcitable following D2 stimulation. Western blotting, in vivo electrophysiology, pharmacological D2 manipulation in genetic knockout mice Molecular psychiatry Medium 20956979
2011 DISC1 aggresomes recruit dysbindin via a direct interaction mapped to DISC1 residues 316–597 and dysbindin residues 82–173; direct interaction between soluble DISC1 and dysbindin is demonstrated in a cell-free system using E. coli-expressed proteins; co-aggregation of both proteins is found in postmortem brains of mental disease patients but not healthy controls. Cell transfection aggresome assay, E. coli recombinant protein binding assay, postmortem brain biochemical fractionation and co-immunoprecipitation Biological psychiatry Medium 21531389
2011 Dysbindin assembles into BLOC-1, which interacts with AP-3; BLOC-1/AP-3 deficiencies reduce PI4KIIα content in the dentate gyrus of dysbindin-null mice due to a failure to traffic PI4KIIα from cell bodies to neurites, defining a BLOC-1/AP-3-dependent vesicle transport mechanism for cargo sorting from neuronal cell bodies to nerve terminals. Co-purification, AP-3 and BLOC-1 knockout mouse analysis, immunofluorescence in primary neurons and PC12 cells, AP-3 sorting motif mutagenesis Molecular biology of the cell High 21998198
2011 Dysbindin-1 isoforms show distinct subsynaptic localizations: dysbindin-1B is predominantly associated with synaptic vesicles, while dysbindin-1A and -1C are predominantly in postsynaptic densities, as determined by Western blotting of subsynaptic tissue fractions. Subcellular fractionation, Western blotting of subsynaptic fractions from multiple brain areas PloS one Medium 21390302
2011 Dysbindin-1 recruits necdin to the cytoplasm, attenuating necdin's repression of p53 transcriptional activity; dysbindin-1 knockdown reduces p53 target genes coronin 1b and rab13, impairing neurite outgrowth; overexpression of p53 rescues neurite outgrowth blocked by dysbindin-1 knockdown; sandy mouse neurons show reduced p21, coronin 1b, and rab13 and neurite outgrowth defects. Yeast two-hybrid, co-immunoprecipitation, siRNA knockdown, p53 reporter assay, neurite outgrowth imaging in primary neurons from sdy mice Molecular psychiatry Medium 21502952
2011 Drosophila dysbindin (Ddysb) reduced in presynaptic neurons suppresses glutamatergic synaptic transmission causing memory impairment; reduced Ddysb in glial cells causes hyperdopaminergic activity by altering expression of the dopamine metabolic enzyme Ebony, leading to abnormal locomotion. Cell-type-specific RNAi (neuronal vs. glial), electrophysiology, behavioral assays, Ebony expression analysis in Drosophila Proceedings of the National Academy of Sciences of the United States of America High 22049342
2013 Dysbindin binds RhoA and activates RhoA-SRF and MEK1-ERK1 signaling pathways in cardiomyocytes, inducing cardiac hypertrophy; RhoA was identified as a novel dysbindin-binding partner by yeast two-hybrid and confirmed by co-immunoprecipitation. Yeast two-hybrid, co-immunoprecipitation, SRF luciferase reporter assay, Western blotting, morphological hypertrophy measurements in neonatal rat cardiomyocytes The Journal of cell biology Medium 24385487
2013 Dysbindin-1 null (sdy) mice show reduced NMDAR-dependent LTP in hippocampal CA1 that is rescued by exogenous glycine (NMDAR co-agonist), indicating impaired NMDAR function underlies the plasticity deficit; homozygous null mice also show deficits in contextual fear conditioning. Hippocampal slice field recordings (LTP), pharmacological rescue with glycine, contextual fear conditioning in genetic null mice Hippocampus Medium 24446171
2013 Dysbindin-1 null mice have a decreased readily releasable pool of synaptic vesicles, decreased quantal size, decreased release probability, deficits in endo- and exocytosis rates, decreased intracellular Ca2+, reduced expression of L- and N-type Ca2+ channels, and reduced expression of synaptic vesicle trafficking and priming proteins in PFC. Electrophysiology, vesicle imaging, calcium imaging, Western blotting in dysbindin-null mice Schizophrenia research Medium 23473812
2014 Dysbindin-1C isoform (but not -1A) is specifically localized to hilar glutamatergic mossy cells in dentate gyrus; loss of dysbindin-1C (in sdy mice) reduces mossy cell numbers and causes delayed maturation of adult-born neurons, whereas muted mice (in which dysbindin-1A is destabilized but -1C is intact) do not show this phenotype. Immunohistochemistry for isoform-specific localization, comparison of sdy and muted mouse hippocampal phenotypes, BrdU/doublecortin labeling for neurogenesis The Journal of biological chemistry Medium 25157109
2014 Dysbindin-null neurons show hyperactive dendritic protrusion dynamics (increased formation, retraction, and conversion); CaMKIIα is required for mushroom/thin spine stabilization; the hyperactivity in dysbindin-null neurons is attributed in part to decreased CaMKIIα activity resulting from increased Abi1-mediated inhibition of CaMKIIα. Time-lapse live imaging of hippocampal neurons from dysbindin-null mice, CaMKIIα activity assays, Abi1 co-immunoprecipitation The Journal of neuroscience Medium 25297099
2015 Dysbindin-1 deficiency reduces BDNF exocytosis from cortical excitatory neurons (measured by TIRF microscopy); this reduction in BDNF release transsynaptically decreases the number of inhibitory synapses on excitatory neurons; exogenous BDNF rescues the inhibitory synaptic deficits caused by reduced dysbindin-1 in cultured neurons and slice cultures. TIRF microscopy (live-cell BDNF exocytosis imaging), whole-cell recordings, immunohistochemistry, exogenous BDNF rescue in cortical neurons and organotypic slices Biological psychiatry High 26386481
2015 Dysbindin/BLOC-1 deficiency reduces expression of Arp2/3 complex subunits in neuronal cells, impairs actin dynamics in early endosomes, and Arp2/3, dysbindin, and BLOC-1 subunits biochemically and genetically interact in Drosophila to modulate synapse morphology and homeostatic plasticity. Quantitative mass spectrometry proteomics, Western blot validation, actin dynamics assay, co-immunoprecipitation, Drosophila genetic interaction (synapse morphology and electrophysiology) The Journal of neuroscience High 27927957
2015 Dysbindin/BLOC-1 genetically and biochemically interacts with the copper transporter ATP7A; BLOC-1-null mice show altered transcriptional profiles of copper-regulatory and dependent factors in hippocampus; dysbindin/BLOC-1 loss-of-function alleles increase susceptibility to toxic copper challenges in mammalian cells and Drosophila without changing basal copper content. Co-immunoprecipitation, transcriptomic analysis in BLOC-1-null mice, copper toxicity assays in cells and Drosophila, genetic interaction analysis Human molecular genetics Medium 26199316
2015 N-ethylmaleimide-sensitive factor (NSF) protein levels are downregulated in dysbindin/BLOC-1-deficient cells; human dysbindin/BLOC-1 co-precipitates with NSF; in Drosophila, presynaptic expression of either dysbindin or NSF fully rescues the dysbindin-mutant failure of homeostatic synaptic plasticity. Proteome-wide screen, co-immunoprecipitation, Drosophila genetic rescue of homeostatic plasticity (electrophysiology) The Journal of neuroscience Medium 25972187
2017 TRIM24 binds dysbindin (identified by yeast two-hybrid, confirmed by co-IP) and protects dysbindin from TRIM32-mediated degradation in cardiomyocytes; TRIM32 degrades dysbindin in cardiomyocytes (as in skeletal muscle), attenuating dysbindin-driven SRF signaling and hypertrophy; TRIM24 overexpression promotes dysbindin-dependent SRF activation and hypertrophy. Yeast two-hybrid, co-immunoprecipitation, co-immunostaining, Western blotting for dysbindin levels after TRIM24/TRIM32 manipulation, SRF luciferase reporter assay, cardiomyocyte hypertrophy measurements The Journal of biological chemistry Medium 28465353
2018 Dysbindin regulates access to EGTA-sensitive (loosely coupled) synaptic vesicles; presynaptic proteasome inhibition potentiates release under baseline conditions but not during homeostatic plasticity, and this effect requires dysbindin; genetic evidence indicates dysbindin levels control the pool of low-release-probability vesicles recruited during homeostatic plasticity at the Drosophila NMJ. Drosophila NMJ electrophysiology, pharmacological proteasome inhibition, EGTA sensitivity assays, genetic epistasis with dysbindin mutants Nature communications Medium 29348419
2018 Genetic variants reducing dysbindin-1 expression alter cognitive response to antipsychotics through an imbalance between short and long isoforms of dopamine D2 receptors, leading to enhanced presynaptic D2 function within the prefrontal cortex; this was demonstrated in postmortem human brains and genetically modified mice. Postmortem human brain analysis, genetically modified mice, D2 receptor isoform quantification, behavioral pharmacology Nature communications Medium 29891954
2008 siRNA knockdown of dysbindin in SH-SY5Y cells causes aberrant actin cytoskeleton organization; growth cones of hippocampal neurons from sandy mice show similar morphological abnormalities; dysbindin expression level correlates with JNK phosphorylation, suggesting dysbindin regulates JNK signaling and actin cytoskeleton organization. siRNA knockdown, phalloidin/immunofluorescence for actin morphology, Western blotting for pJNK in cell lines and primary neurons from sdy mice Biochemical and biophysical research communications Low 19094965

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia. American journal of human genetics 623 12098102
2004 Evidence of novel neuronal functions of dysbindin, a susceptibility gene for schizophrenia. Human molecular genetics 280 15345706
2001 Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain. The Journal of biological chemistry 254 11316798
2009 The schizophrenia susceptibility gene dysbindin controls synaptic homeostasis. Science (New York, N.Y.) 181 19965435
2003 The DTNBP1 (dysbindin) gene contributes to schizophrenia, depending on family history of the disease. American journal of human genetics 160 14618545
2005 Haplotypes at the dystrobrevin binding protein 1 (DTNBP1) gene locus mediate risk for schizophrenia through reduced DTNBP1 expression. Human molecular genetics 150 15917270
2004 Identification in 2 independent samples of a novel schizophrenia risk haplotype of the dystrobrevin binding protein gene (DTNBP1). Archives of general psychiatry 147 15066891
2006 Genetic variation in DTNBP1 influences general cognitive ability. Human molecular genetics 134 16415041
2004 Association of the DTNBP1 locus with schizophrenia in a U.S. population. American journal of human genetics 134 15362017
2008 DTNBP1, a schizophrenia susceptibility gene, affects kinetics of transmitter release. The Journal of cell biology 129 18504299
2006 Dysbindin-1 is a synaptic and microtubular protein that binds brain snapin. Human molecular genetics 128 16980328
2009 Role of dysbindin in dopamine receptor trafficking and cortical GABA function. Proceedings of the National Academy of Sciences of the United States of America 125 19887632
2004 Strong evidence for association between the dystrobrevin binding protein 1 gene (DTNBP1) and schizophrenia in 488 parent-offspring trios from Bulgaria. Biological psychiatry 122 15121479
2005 Relationship between a high-risk haplotype in the DTNBP1 (dysbindin) gene and clinical features of schizophrenia. The American journal of psychiatry 120 16199828
2003 Identification of a high-risk haplotype for the dystrobrevin binding protein 1 (DTNBP1) gene in the Irish study of high-density schizophrenia families. Molecular psychiatry 118 12808430
2010 Dysbindin-1 modulates prefrontal cortical activity and schizophrenia-like behaviors via dopamine/D2 pathways. Molecular psychiatry 117 20956979
2007 Evidence that the BLOC-1 protein dysbindin modulates dopamine D2 receptor internalization and signaling but not D1 internalization. The Journal of neuroscience : the official journal of the Society for Neuroscience 113 17989303
2009 TRIM32 is an E3 ubiquitin ligase for dysbindin. Human molecular genetics 112 19349376
2007 Reduced DTNBP1 (dysbindin-1) mRNA in the hippocampal formation of schizophrenia patients. Schizophrenia research 110 17961984
2008 Dysbindin deficiency in sandy mice causes reduction of snapin and displays behaviors related to schizophrenia. Schizophrenia research 105 18774265
2009 Dysbindin-1 in dorsolateral prefrontal cortex of schizophrenia cases is reduced in an isoform-specific manner unrelated to dysbindin-1 mRNA expression. Human molecular genetics 98 19617633
2008 Impaired long-term memory retention and working memory in sdy mutant mice with a deletion in Dtnbp1, a susceptibility gene for schizophrenia. Molecular brain 98 18945333
2010 Reduced dysbindin expression mediates N-methyl-D-aspartate receptor hypofunction and impaired working memory performance. Biological psychiatry 87 21035792
2006 Dysbindin genotype and negative symptoms in schizophrenia. The American journal of psychiatry 87 16513878
2009 Dysbindin regulates hippocampal LTP by controlling NMDA receptor surface expression. Proceedings of the National Academy of Sciences of the United States of America 86 19955431
2010 Dysbindin-1, WAVE2 and Abi-1 form a complex that regulates dendritic spine formation. Molecular psychiatry 81 20531346
2008 Behavioral abnormalities and dopamine reductions in sdy mutant mice with a deletion in Dtnbp1, a susceptibility gene for schizophrenia. Biochemical and biophysical research communications 81 18555792
2005 Is the dysbindin gene (DTNBP1) a susceptibility gene for schizophrenia? Schizophrenia bulletin 81 16166606
2009 Dysbindin modulates prefrontal cortical glutamatergic circuits and working memory function in mice. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 79 19641486
2005 Bipolar disorder and polymorphisms in the dysbindin gene (DTNBP1). Biological psychiatry 77 15820225
2003 No evidence for association of the dysbindin gene [DTNBP1] with schizophrenia in an Irish population-based study. Schizophrenia research 73 12591580
2006 DTNBP1 (dysbindin) gene variants modulate prefrontal brain function in healthy individuals. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 72 16407900
2006 Analysis of high-resolution HapMap of DTNBP1 (Dysbindin) suggests no consistency between reported common variant associations and schizophrenia. American journal of human genetics 71 17033966
2007 Association of schizophrenia with DTNBP1 but not with DAO, DAOA, NRG1 and RGS4 nor their genetic interaction. Journal of psychiatric research 67 17408693
2011 Synaptic dysbindin-1 reductions in schizophrenia occur in an isoform-specific manner indicating their subsynaptic location. PloS one 66 21390302
2005 Dysbindin (DTNBP1, 6p22.3) is associated with childhood-onset psychosis and endophenotypes measured by the Premorbid Adjustment Scale (PAS). Journal of autism and developmental disorders 65 16283082
2011 Cell biology of the BLOC-1 complex subunit dysbindin, a schizophrenia susceptibility gene. Molecular neurobiology 64 21520000
2011 Convergence of two independent mental disease genes on the protein level: recruitment of dysbindin to cell-invasive disrupted-in-schizophrenia 1 aggresomes. Biological psychiatry 64 21531389
2008 Behavioral characterization of dysbindin-1 deficient sandy mice. Behavioural brain research 64 18984010
2011 Dysbindin-containing complexes and their proposed functions in brain: from zero to (too) many in a decade. ASN neuro 63 21504412
2003 Abnormal dysbindin expression in cerebellar mossy fiber synapses in the mdx mouse model of Duchenne muscular dystrophy. The Journal of neuroscience : the official journal of the Society for Neuroscience 62 12878699
2011 The schizophrenia susceptibility factor dysbindin and its associated complex sort cargoes from cell bodies to the synapse. Molecular biology of the cell 61 21998198
2006 Reinvestigation of the dysbindin subunit of BLOC-1 (biogenesis of lysosome-related organelles complex-1) as a dystrobrevin-binding protein. The Biochemical journal 60 16448387
2015 Antipsychotic drugs attenuate aberrant DNA methylation of DTNBP1 (dysbindin) promoter in saliva and post-mortem brain of patients with schizophrenia and Psychotic bipolar disorder. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 58 26285059
2010 Dysbindin promotes the post-endocytic sorting of G protein-coupled receptors to lysosomes. PloS one 56 20174469
2013 Epistatic interaction between COMT and DTNBP1 modulates prefrontal function in mice and in humans. Molecular psychiatry 55 24145376
2003 Myospryn is a novel binding partner for dysbindin in muscle. The Journal of biological chemistry 55 14688250
2009 The sandy (sdy) mouse: a dysbindin-1 mutant relevant to schizophrenia research. Progress in brain research 54 20302821
2007 Early visual processing deficits in dysbindin-associated schizophrenia. Biological psychiatry 53 17945199
2011 Dysbindin-1, a schizophrenia-related protein, facilitates neurite outgrowth by promoting the transcriptional activity of p53. Molecular psychiatry 51 21502952
2007 Association between the DTNBP1 gene and intelligence: a case-control study in young patients with schizophrenia and related disorders and unaffected siblings. Behavioral and brain functions : BBF 51 17445278
2007 Dysbindin (DTNBP1) and the biogenesis of lysosome-related organelles complex 1 (BLOC-1): main and epistatic gene effects are potential contributors to schizophrenia susceptibility. Biological psychiatry 48 17618940
2016 COMT, BDNF, and DTNBP1 polymorphisms and cognitive functions in patients with brain tumors. Neuro-oncology 47 27091610
2007 The role of DTNBP1, NRG1, and AKT1 in the genetics of schizophrenia in Finland. Schizophrenia research 46 17300918
2015 Gene dosage in the dysbindin schizophrenia susceptibility network differentially affect synaptic function and plasticity. The Journal of neuroscience : the official journal of the Society for Neuroscience 45 25568125
2011 Schizophrenia susceptibility gene dysbindin regulates glutamatergic and dopaminergic functions via distinctive mechanisms in Drosophila. Proceedings of the National Academy of Sciences of the United States of America 45 22049342
2006 Effect of antipsychotic drugs on DISC1 and dysbindin expression in mouse frontal cortex and hippocampus. Journal of neural transmission (Vienna, Austria : 1996) 45 16463116
2007 The dysbindin gene (DTNBP1) is associated with methamphetamine psychosis. Biological psychiatry 43 17555717
2008 Variation in the dysbindin gene and normal cognitive function in three independent population samples. Genes, brain, and behavior 42 19077176
2018 Variations in Dysbindin-1 are associated with cognitive response to antipsychotic drug treatment. Nature communications 40 29891954
2017 TRIM24 protein promotes and TRIM32 protein inhibits cardiomyocyte hypertrophy via regulation of dysbindin protein levels. The Journal of biological chemistry 39 28465353
2018 Dysbindin links presynaptic proteasome function to homeostatic recruitment of low release probability vesicles. Nature communications 38 29348419
2017 Dysbindin-1 Involvement in the Etiology of Schizophrenia. International journal of molecular sciences 38 28937620
2007 Association study of dysbindin gene with clinical and outcome measures in a representative cohort of Italian schizophrenic patients. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 38 17290445
2019 The epistatic interaction between the dopamine D3 receptor and dysbindin-1 modulates higher-order cognitive functions in mice and humans. Molecular psychiatry 37 31492942
2008 Dysbindin engages in c-Jun N-terminal kinase activity and cytoskeletal organization. Biochemical and biophysical research communications 37 19094965
2004 Linkage disequlibrium in the DTNBP1 (dysbindin) gene region and on chromosome 1p36 among psychotic patients from a genetic isolate in Israel: findings from identity by descent haplotype sharing analysis. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 36 15211634
2013 MeCP2 regulates the synaptic expression of a Dysbindin-BLOC-1 network component in mouse brain and human induced pluripotent stem cell-derived neurons. PloS one 35 23750231
2010 Cytosolic protein interactions of the schizophrenia susceptibility gene dysbindin. Journal of neurochemistry 34 20236384
2007 DTNBP1 (Dystrobrevin binding protein 1) and schizophrenia: association evidence in the 3' end of the gene. Human heredity 34 17476109
2009 DTNBP1, NRG1, DAOA, DAO and GRM3 polymorphisms and schizophrenia: an association study. Neuropsychobiology 32 19439994
2009 Association of the dystrobrevin binding protein 1 gene (DTNBP1) in a bipolar case-control study (BACCS). American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 31 19089808
2009 The dystrobrevin binding protein 1 (DTNBP1) gene is associated with schizophrenia in the Irish Case Control Study of Schizophrenia (ICCSS) sample. Schizophrenia research 31 19800201
2004 Schizophrenia genetics: dysbindin under the microscope. Trends in neurosciences 31 15331232
2015 Regulation of Brain-Derived Neurotrophic Factor Exocytosis and Gamma-Aminobutyric Acidergic Interneuron Synapse by the Schizophrenia Susceptibility Gene Dysbindin-1. Biological psychiatry 30 26386481
2014 Mutations in the BLOC-1 subunits dysbindin and muted generate divergent and dosage-dependent phenotypes. The Journal of biological chemistry 30 24713699
2006 Association study of the dysbindin (DTNBP1) gene in schizophrenia from the Japanese population. Neuroscience research 30 16876895
2010 Analysis of HapMap tag-SNPs in dysbindin (DTNBP1) reveals evidence of consistent association with schizophrenia. European psychiatry : the journal of the Association of European Psychiatrists 29 20615671
2010 Meta-analysis of genetic variation in DTNBP1 and general cognitive ability. Biological psychiatry 29 21130223
2015 The N-ethylmaleimide-sensitive factor and dysbindin interact to modulate synaptic plasticity. The Journal of neuroscience : the official journal of the Society for Neuroscience 28 25972187
2013 Potential molecular mechanisms for decreased synaptic glutamate release in dysbindin-1 mutant mice. Schizophrenia research 28 23473812
2013 Dysbindin is a potent inducer of RhoA-SRF-mediated cardiomyocyte hypertrophy. The Journal of cell biology 28 24385487
2013 Dysbindin-1 loss compromises NMDAR-dependent synaptic plasticity and contextual fear conditioning. Hippocampus 28 24446171
2007 Association study between the dystrobrevin binding protein 1 gene (DTNBP1) and schizophrenia: a meta-analysis. Schizophrenia research 28 17604607
2016 The Proteome of BLOC-1 Genetic Defects Identifies the Arp2/3 Actin Polymerization Complex to Function Downstream of the Schizophrenia Susceptibility Factor Dysbindin at the Synapse. The Journal of neuroscience : the official journal of the Society for Neuroscience 27 27927957
2014 The schizophrenia susceptibility gene dysbindin regulates dendritic spine dynamics. The Journal of neuroscience : the official journal of the Society for Neuroscience 27 25297099
2015 Loss of dysbindin-1, a risk gene for schizophrenia, leads to impaired group 1 metabotropic glutamate receptor function in mice. Frontiers in behavioral neuroscience 26 25859193
2014 Dysbindin-1C is required for the survival of hilar mossy cells and the maturation of adult newborn neurons in dentate gyrus. The Journal of biological chemistry 26 25157109
2009 Direct interaction of Dysbindin with the AP-3 complex via its mu subunit. Neurochemistry international 26 19428785
2015 Neuronal copper homeostasis susceptibility by genetic defects in dysbindin, a schizophrenia susceptibility factor. Human molecular genetics 25 26199316
2013 Microsatellite markers as a rapid approach for autozygosity mapping in Hermansky-Pudlak syndrome: identification of the second HPS7 mutation in a patient presenting late in life. Thrombosis and haemostasis 25 23364359
2009 Association between the dysbindin gene (DTNBP1) and cognitive functions in Japanese subjects. Psychiatry and clinical neurosciences 25 19496996
2009 Proteomic analysis reveals novel binding partners of dysbindin, a schizophrenia-related protein. Journal of neurochemistry 25 19573021
2007 Effect of 5-haplotype of dysbindin gene (DTNBP1) polymorphisms for the susceptibility to bipolar I disorder. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 25 17192893
2015 Dysbindin (DTNBP1) variants are associated with hallucinations in schizophrenia. European psychiatry : the journal of the Association of European Psychiatrists 23 25697573
2009 Dysbindin gene (DTNBP1) in major depression: association with clinical response to selective serotonin reuptake inhibitors. Pharmacogenetics and genomics 23 19065121
2009 The efficacies of clozapine and haloperidol in refractory schizophrenia are related to DTNBP1 variation. Pharmacogenetics and genomics 23 19369910
2009 DTNBP1 is associated with imaging phenotypes in schizophrenia. Human brain mapping 23 19449336
2010 Nucleocytoplasmic shuttling of dysbindin-1, a schizophrenia-related protein, regulates synapsin I expression. The Journal of biological chemistry 22 20921223
2006 The dysbindin gene (DTNBP1) and schizophrenia: no support for an association in the Korean population. Neuroscience letters 22 16959423

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