Affinage

DTNBP1

Dysbindin · UniProt Q96EV8

Length
351 aa
Mass
39.5 kDa
Annotated
2026-04-28
100 papers in source corpus 39 papers cited in narrative 39 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

DTNBP1 (dysbindin) is a coiled-coil protein that functions as a core subunit of the BLOC-1 complex to regulate vesicle trafficking from endosomes to lysosome-related organelles and from neuronal cell bodies to synapses, with loss-of-function mutations causing Hermansky-Pudlak syndrome type 7 (PMID:12923531). At the presynapse, dysbindin controls synaptic vesicle biogenesis, the size of the readily releasable pool, quantal release, and exocytosis of glutamate and BDNF, and is required for homeostatic synaptic plasticity through a mechanism involving NSF and acting downstream or independently of calcium influx (PMID:18504299, PMID:19965435, PMID:25972187, PMID:26386481). Postsynaptically, dysbindin regulates surface expression of NR2A-containing NMDA receptors to modulate LTP and directs D2 dopamine receptor sorting to lysosomes, thereby controlling GABAergic interneuron excitability in prefrontal cortex (PMID:19955431, PMID:19887632). Dysbindin protein levels are regulated by TRIM32-mediated ubiquitin-dependent degradation counteracted by TRIM24, and dysbindin undergoes CRM1-dependent nucleocytoplasmic shuttling to control synapsin I transcription (PMID:19349376, PMID:28465353, PMID:20921223).

Mechanistic history

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

    The initial identification of dysbindin as a dystrobrevin-binding coiled-coil protein established it as a component of the dystrophin-associated protein complex in muscle and brain, localizing it to synaptic terminals.

    Evidence Yeast two-hybrid, reciprocal co-immunoprecipitation, and immunofluorescence in muscle and brain tissue

    PMID:11316798

    Open questions at the time
    • Functional consequence of the dystrobrevin interaction was unknown
    • Whether dysbindin operated independently of the DPC was unresolved
  2. 2003 High

    Discovery that dysbindin is an obligate subunit of BLOC-1 and that its loss causes Hermansky-Pudlak syndrome type 7 reframed dysbindin from a DPC component to a vesicle trafficking regulator, and later work showed BLOC-1-assembled dysbindin does not physiologically bind dystrobrevins.

    Evidence Sandy (sdy) mouse model, human HPS-7 mutation analysis, BLOC-1 complex identification; subsequently challenged by recombinant protein and endogenous co-IP experiments

    PMID:12923531 PMID:16448387

    Open questions at the time
    • Specific vesicle trafficking step controlled by dysbindin-BLOC-1 was not defined
    • Brain-specific vs. ubiquitous function of BLOC-1 was unclear
  3. 2004 Medium

    Gain- and loss-of-function studies in cortical neurons established that dysbindin positively regulates presynaptic protein expression (SNAP25, synapsin I) and glutamate release, linking it to excitatory neurotransmission and PI3K-Akt survival signaling.

    Evidence Overexpression and siRNA knockdown in primary cortical neurons with glutamate release assays and Akt phosphorylation readouts

    PMID:15345706

    Open questions at the time
    • Direction of SNAP25 regulation was contradicted by PC12 cell data (PMID:16701550)
    • Whether glutamate release effects were cell-autonomous was untested
  4. 2006 High

    Identification of snapin as a direct synaptic vesicle-associated partner of dysbindin, with immunoelectron microscopy placing dysbindin at synaptic vesicles and postsynaptic densities, provided ultrastructural evidence for its dual pre- and postsynaptic roles.

    Evidence In vitro binding, reciprocal co-IP, subcellular fractionation, and immunoelectron microscopy in mouse hippocampus

    PMID:16980328

    Open questions at the time
    • Functional consequence of the dysbindin-snapin interaction on vesicle release was not tested
  5. 2008 High

    Electrophysiological and ultrastructural analysis of dysbindin-null mice revealed that dysbindin is required for normal vesicle biogenesis, quantal size, release probability, and readily releasable pool size, establishing its direct role in regulated exocytosis.

    Evidence Amperometry, whole-cell patch clamp, and electron microscopy in sdy mouse neuroendocrine cells and hippocampal synapses

    PMID:18504299

    Open questions at the time
    • Molecular intermediates between BLOC-1 and vesicle biogenesis machinery were unknown
    • Whether defects were BLOC-1-dependent was not resolved
  6. 2009 High

    A convergent set of 2009 studies defined dysbindin's postsynaptic functions: it controls surface expression of D2 dopamine receptors (via post-endocytic lysosomal sorting) and NR2A-containing NMDA receptors, thereby modulating GABAergic interneuron excitability and hippocampal LTP, respectively. Concurrently, a Drosophila forward genetic screen established dysbindin as essential for presynaptic homeostatic synaptic plasticity.

    Evidence Surface biotinylation, receptor trafficking, and electrophysiology in dys−/− mice (D2R and NR2A); unbiased electrophysiology-based screen plus epistasis at Drosophila NMJ

    PMID:19887632 PMID:19955431 PMID:19965435 PMID:20174469

    Open questions at the time
    • Mechanism by which dysbindin directs receptor-specific sorting remained unclear
    • Identity of the calcium-independent step in homeostatic plasticity was not resolved
  7. 2009 High

    TRIM32 was identified as the E3 ubiquitin ligase that ubiquitinates and targets dysbindin for proteasomal degradation, with LGMD2H-associated TRIM32 mutations impairing this activity, connecting dysbindin turnover to muscle disease.

    Evidence Yeast two-hybrid, in vitro ubiquitination assay, siRNA knockdown in myoblasts, mutagenesis of disease-associated TRIM32 alleles

    PMID:19349376

    Open questions at the time
    • Whether TRIM32-mediated regulation of dysbindin occurs in neurons was untested
    • Physiological consequence of elevated dysbindin in TRIM32 mutant muscle was not shown
  8. 2009 Medium

    Direct interactions of BLOC-1/dysbindin with AP-3 adaptor, SNARE proteins (SNAP-25, syntaxin 13), and Munc18-1 placed the complex within the molecular machinery of vesicle sorting and fusion, and revealed neurite outgrowth as a BLOC-1-dependent developmental process.

    Evidence Co-immunoprecipitation, direct binding assays, affinity chromatography/mass spectrometry, neurite outgrowth assays in BLOC-1-deficient neurons

    PMID:19428785 PMID:19546860 PMID:19573021

    Open questions at the time
    • Hierarchy among AP-3, SNARE, and Munc18-1 interactions was not established
    • Whether neurite outgrowth defects are BLOC-1-specific or a general SNARE trafficking phenotype was unclear
  9. 2010 Medium

    Dysbindin was found to undergo CRM1-dependent nucleocytoplasmic shuttling and to regulate synapsin I transcription from the nucleus, revealing a non-canonical nuclear function beyond vesicle trafficking.

    Evidence Leptomycin B treatment, NES mutagenesis, qPCR and Western blot for synapsin I in sdy mice

    PMID:20921223

    Open questions at the time
    • The transcription factor(s) or chromatin targets mediating synapsin I regulation were not identified
    • Fraction of dysbindin in nucleus vs. cytoplasm under physiological conditions was not quantified
  10. 2011 High

    BLOC-1/AP-3-dependent sorting was shown to deliver specific cargo (PI4KIIα) from neuronal cell bodies to synapses, providing a concrete example of how dysbindin-containing BLOC-1 controls synaptic protein composition.

    Evidence Co-purification of PI4KIIα with BLOC-1/AP-3, reduced PI4KIIα in dentate gyrus of dysbindin-null and AP-3-null mice, neurite trafficking assay

    PMID:21998198

    Open questions at the time
    • Full repertoire of BLOC-1/AP-3-dependent synaptic cargoes was not defined
    • Whether PI4KIIα loss accounts for synaptic vesicle biogenesis defects was unknown
  11. 2015 High

    NSF was identified as a key effector downstream of dysbindin/BLOC-1: NSF is downregulated by BLOC-1 deficiency, and presynaptic NSF expression fully rescues the homeostatic plasticity defect in Drosophila dysbindin mutants, establishing a mechanistic link between BLOC-1 and SNARE-dependent membrane fusion.

    Evidence Quantitative proteomics, co-immunoprecipitation, genetic rescue experiment with electrophysiology at Drosophila NMJ

    PMID:25972187

    Open questions at the time
    • Whether NSF rescue reflects restored vesicle fusion per se or secondary effects on vesicle pools was not distinguished
    • Mammalian validation of the NSF rescue was lacking
  12. 2015 High

    TIRF microscopy demonstrated that dysbindin loss specifically reduces BDNF exocytosis from excitatory neurons, which transsynaptically decreases inhibitory synapse formation — a circuit-level mechanism linking dysbindin to excitatory-inhibitory balance.

    Evidence TIRF live imaging of BDNF vesicle fusion, electrophysiology, immunohistochemistry, and BDNF rescue in dysbindin mutant cortical neurons and slices

    PMID:26386481

    Open questions at the time
    • Whether BDNF exocytosis defect is BLOC-1-dependent or involves a BLOC-1-independent dysbindin function was not resolved
  13. 2016 High

    The Arp2/3 actin polymerization complex was placed downstream of BLOC-1 as a regulator of endosomal actin dynamics, synapse morphology, and homeostatic plasticity, integrating dysbindin's vesicle trafficking function with actin cytoskeletal remodeling.

    Evidence Quantitative mass spectrometry, co-immunoprecipitation, Drosophila genetic interaction, endosomal actin dynamics assay

    PMID:27927957

    Open questions at the time
    • Direct vs. indirect regulation of Arp2/3 by BLOC-1 was not resolved
    • How Arp2/3-dependent actin remodeling connects to vesicle biogenesis defects was untested
  14. 2017 Medium

    TRIM24 was identified as a protective factor that counteracts TRIM32-mediated degradation of dysbindin in cardiomyocytes, linking dysbindin stability to SRF-dependent hypertrophic signaling in the heart.

    Evidence Yeast two-hybrid, co-immunoprecipitation, overexpression/knockdown in neonatal cardiomyocytes, SRF reporter assay

    PMID:28465353

    Open questions at the time
    • Whether TRIM24-TRIM32 competition for dysbindin occurs in neurons was not tested
    • Structural basis for competitive binding was not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the full cargo repertoire of BLOC-1/AP-3-dependent sorting in neurons; the transcriptional mechanism by which nuclear dysbindin regulates synapsin I; whether BLOC-1-dependent and BLOC-1-independent functions of dysbindin can be cleanly separated in vivo; and the structural basis for dysbindin's assembly into BLOC-1 and its interaction with diverse partners.
  • No high-resolution structure of dysbindin or BLOC-1 with dysbindin
  • Nuclear transcriptional targets beyond synapsin I are undefined
  • Separation of BLOC-1-dependent vs. independent functions in mammalian neurons not achieved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0031410 cytoplasmic vesicle 3 GO:0005768 endosome 2 GO:0005829 cytosol 2 GO:0005634 nucleus 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-162582 Signal Transduction 3 R-HSA-392499 Metabolism of proteins 2
Partners
AP3B1MUNC18-1MUTEDNSFPLDNSNAPINTRIM24TRIM32
Complex memberships
BLOC-1

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2001 Dysbindin (DTNBP1) was identified as a novel coiled-coil-containing protein that binds directly to alpha- and beta-dystrobrevin in muscle and brain via yeast two-hybrid screen; dystrophin and alpha-dystrobrevin are co-immunoprecipitated with dysbindin, indicating dysbindin is a component of the dystrophin-associated protein complex (DPC). In brain, dysbindin localizes primarily to axon bundles and mossy fiber synaptic terminals in the cerebellum and hippocampus. Yeast two-hybrid screen, co-immunoprecipitation, co-localization by immunofluorescence The Journal of biological chemistry High 11316798
2003 Dysbindin is a component of the biogenesis of lysosome-related organelles complex 1 (BLOC-1), which includes pallidin, muted, and cappuccino. Mutant sandy (sdy) mice lack dysbindin protein due to a deletion in Dtnbp1, and mutations in human DTNBP1 cause Hermansky-Pudlak syndrome type 7 (HPS-7), demonstrating dysbindin's role in vesicle trafficking to lysosome-related organelles such as melanosomes and platelet dense granules. Mouse genetic deletion model, protein complex identification, human mutation analysis Nature genetics High 12923531
2003 Dysbindin binds to myospryn, a novel 413-kDa protein expressed in cardiac and skeletal muscle. Dysbindin and myospryn co-immunoprecipitate from muscle extracts and are extensively co-localized, identifying a tissue-specific ligand for dysbindin in muscle. Yeast two-hybrid screen, co-immunoprecipitation, co-localization by immunofluorescence The Journal of biological chemistry Medium 14688250
2004 Overexpression of dysbindin in primary cortical neurons increased expression of pre-synaptic proteins SNAP25 and synapsin I, and increased extracellular basal glutamate levels and evoked glutamate release. Conversely, siRNA-mediated knockdown reduced pre-synaptic protein expression and glutamate release, indicating dysbindin influences exocytotic glutamate release. Dysbindin overexpression also increased Akt phosphorylation and protected neurons against death via PI3-kinase-Akt signaling; siRNA knockdown diminished Akt phosphorylation and facilitated neuronal death. Neuronal overexpression, siRNA knockdown, glutamate release assay, Western blot for Akt phosphorylation, pharmacological inhibition (LY294002) Human molecular genetics Medium 15345706
2006 Dysbindin-1 co-localizes with snapin at synaptic vesicle membranes and postsynaptic densities in mouse brain and human hippocampus. Snapin was identified as a direct binding partner of dysbindin-1 in vitro and in the brain by co-immunoprecipitation and tissue fractionation. Immunoelectron microscopy showed dysbindin-1 in synaptic vesicles of axospinous terminals and postsynaptic densities and microtubules of hippocampal neurons. Co-immunoprecipitation, tissue fractionation, immunoelectron microscopy, in vitro binding assay Human molecular genetics High 16980328
2006 Within the BLOC-1 complex, dysbindin's coiled-coil region (a 69-residue segment) contains binding sites for pallidin, snapin, and muted BLOC-1 subunits. Recombinant dystrobrevin coiled-coil proteins failed to bind endogenous BLOC-1 from brain or muscle, and immunoprecipitation of endogenous dysbindin showed no co-immunoprecipitation of dystrobrevin isoforms, indicating that dysbindin assembled into BLOC-1 is not a physiological binding partner of dystrobrevins in vivo. Yeast two-hybrid, recombinant protein binding assays, co-immunoprecipitation from brain and muscle The Biochemical journal High 16448387
2006 Knockdown of dysbindin expression in PC12 cells increased SNAP25 expression and dopamine release, while overexpression of dysbindin decreased SNAP25 expression, suggesting dysbindin negatively regulates dopamine release via modulation of SNAP25. siRNA knockdown, overexpression, dopamine release assay, Western blot Biochemical and biophysical research communications Medium 16701550
2008 In dysbindin-null (sdy) mice, neuroendocrine cells and hippocampal synapses exhibit specific defects in neurosecretion: larger vesicle size, slower quantal vesicle release, lower release probability, and a smaller readily releasable vesicle pool. These findings demonstrate that dysbindin functions to regulate exocytosis and vesicle biogenesis. Amperometry, whole-cell patch clamping, electron microscopy in dysbindin-null sdy mice The Journal of cell biology High 18504299
2008 In sdy mice (dysbindin-null), steady-state levels of snapin were reduced. A 30-residue peptide in dysbindin (residues 90-119) mediates the interaction with snapin, and loss of dysbindin destabilizes snapin, suggesting dysbindin stabilizes snapin to regulate neurotransmission. Western blot in sdy mice, peptide binding assay defining interaction domain Schizophrenia research Medium 18774265
2009 TRIM32 is an E3 ubiquitin ligase that binds and ubiquitinates dysbindin, targeting it for proteasomal degradation. TRIM32 binds dysbindin via yeast two-hybrid and augments its degradation; siRNA knockdown of TRIM32 in myoblasts elevated dysbindin levels. LGMD2H/STM-associated TRIM32 mutations (D487N and R394H) impair ubiquitin ligase activity toward dysbindin and are mislocalized; D487N binds dysbindin and its E2 enzyme but is defective in monoubiquitination. Yeast two-hybrid, co-immunoprecipitation, ubiquitination assay, siRNA knockdown, mutagenesis Human molecular genetics High 19349376
2009 Dysbindin regulates the surface expression of D2 dopamine receptors in cortical neurons. Loss of dysbindin (dys-/-) causes a robust increase in D2 (but not D1) receptor surface expression due to enhanced receptor recycling and insertion rather than reduced endocytosis. Dysbindin-null mice show decreased excitability of fast-spiking GABAergic interneurons in prefrontal cortex and striatum, and decreased inhibitory input to pyramidal neurons. Cell imaging, biochemical surface biotinylation, electrophysiology in dysbindin-knockout mice Proceedings of the National Academy of Sciences of the United States of America High 19887632
2009 Dysbindin controls hippocampal LTP by selectively regulating the surface expression of NMDA receptor subunit NR2A (but not NR2B). In dysbindin-null (Dys-/-) hippocampal neurons, surface NR2A expression is markedly increased, NR2A-mediated synaptic currents are enhanced, and LTP is augmented, while basal synaptic transmission, presynaptic properties, and LTD are normal. Exogenous dysbindin expression reduces NR2A surface expression. Imaging, biotinylation, electrophysiology (LTP, LTD, synaptic currents) in dysbindin-null mice, exogenous dysbindin expression Proceedings of the National Academy of Sciences of the United States of America High 19955431
2009 Dysbindin is required presynaptically for retrograde homeostatic modulation of neurotransmission in Drosophila, functioning in a dose-dependent manner downstream or independently of calcium influx. Identified via electrophysiology-based forward genetic screen of >250 neuronally expressed genes. Forward genetic screen, electrophysiology at Drosophila NMJ, genetic epistasis Science (New York, N.Y.) High 19965435
2009 Brain BLOC-1 (the dysbindin-containing complex) biochemically interacts with a subset of SNARE proteins including SNAP-25 and syntaxin 13. Primary hippocampal neurons deficient in BLOC-1 display neurite outgrowth defects, indicating a role for the dysbindin-BLOC-1 complex in neurodevelopment. Co-immunoprecipitation, primary neuron culture with BLOC-1 deficiency, neurite outgrowth assay Molecular psychiatry Medium 19546860
2009 Dysbindin directly interacts with the mu subunit of the AP-3 adaptor protein complex, as determined by co-immunoprecipitation and direct binding assay. Dysbindin partially co-localizes with AP-3 complex in mouse hippocampus and at presynaptic terminals. Suppression of dysbindin reduces presynaptic protein expression and glutamate release. Co-immunoprecipitation, direct binding assay, siRNA knockdown, glutamate release assay Neurochemistry international Medium 19428785
2009 Dysbindin interacts with Munc18-1 (a synaptic vesicle exocytosis regulator). Munc18-1 was co-immunoprecipitated with dysbindin from rat brain lysate and shown to directly interact with dysbindin in vitro. Part of dysbindin co-localizes with Munc18-1 at presynaptic terminals in hippocampal neurons. Affinity chromatography, mass spectrometry, co-immunoprecipitation, in vitro binding assay, co-localization Journal of neurochemistry Medium 19573021
2009 Dysbindin promotes the post-endocytic sorting of specific GPCRs (D2 dopamine receptor, delta opioid receptor) to lysosomes. Dysbindin knockdown specifically reduced the trafficking of internalized D2 receptors to lysosomes (not endocytosis per se), increasing surface D2 expression. Dysbindin co-immunoprecipitated with GASP-1 and HRS (ESCRT component). RNA interference in HEK293 and HeLa cells, receptor trafficking assays (immunochemical, biochemical), co-immunoprecipitation PloS one Medium 20174469
2009 Dysbindin engages in c-Jun N-terminal kinase (JNK) activity regulation and actin cytoskeletal organization. siRNA-mediated knockdown of dysbindin in SH-SY5Y cells caused aberrant actin cytoskeleton organization; similar morphological abnormalities were observed in growth cones of sdy mouse hippocampal neurons. Dysbindin expression level correlates with JNK phosphorylation level. siRNA knockdown, immunofluorescence for actin, Western blot for p-JNK in cell lines and primary neurons from sdy mice Biochemical and biophysical research communications Medium 19094965
2010 Dysbindin-1 regulates D2-receptor trafficking, and dysbindin-null (dys-/-) mice show altered CaMKII and CaMKKβ expression in medial prefrontal cortex. Dys-/- pyramidal neurons in mPFC are hyperexcitable at baseline but hypoexcitable following D2 stimulation. These effects are reproduced by chronic D2 agonist treatment. Electrophysiology, Western blot, pharmacological treatment in dysbindin-null mice Molecular psychiatry Medium 20956979
2010 Dysbindin-1 forms a ternary complex with WAVE2 and Abi-1. Dysbindin-1 binds WAVE2 (but not N-WASP) as identified by co-immunoprecipitation. Dysbindin-1 promotes the binding of WAVE2 to Abi-1. siRNA knockdown of dysbindin-1 in hippocampal neurons leads to generation of abnormally elongated immature dendritic protrusions, indicating a role in dendritic spine morphogenesis. Co-immunoprecipitation, siRNA knockdown, immunofluorescence, dendritic spine morphology analysis Molecular psychiatry Medium 20531346
2010 Dysbindin-1 is a nucleocytoplasmic shuttling protein with a functional nuclear export signal (NES) mediating CRM1-dependent nuclear export (blocked by leptomycin B). Nuclear shuttling of dysbindin-1 regulates synapsin I expression; in sdy (dysbindin-null) mice, synapsin I protein and mRNA levels are reduced. Nuclear export inhibition (leptomycin B), NES mutagenesis, Western blot, qPCR in sdy mice The Journal of biological chemistry Medium 20921223
2011 Dysbindin interacts directly with DISC1 (disrupted-in-schizophrenia 1). DISC1 aggresomes recruit dysbindin in neuroblastoma cells; domains involved map to DISC1 (residues 316-597) and dysbindin (residues 82-173). A direct interaction between soluble DISC1 and dysbindin was demonstrated in a cell-free system using E. coli-expressed proteins. Co-aggregation of DISC1 and dysbindin was found in postmortem brains of a subgroup of patients with chronic mental disease. Recombinant protein interaction (cell-free), co-expression in neuroblastoma cells, domain mapping, postmortem brain biochemistry Biological psychiatry Medium 21531389
2011 Dysbindin and its BLOC-1 complex sort cargo from neuronal cell bodies to the synapse. PI4KIIα copurified with BLOC-1 and AP-3 in neuronal cells; PI4KIIα content is decreased in the dentate gyrus of dysbindin-null and AP-3-null mice due to failure to traffic from the cell body. In primary cortical neurons lacking AP-3 or BLOC-1, PI4KIIα fails to reach neurites. Co-purification, Western blot in null mice, primary neuron trafficking assay, PC12 cell sorting assay Molecular biology of the cell High 21998198
2011 Dysbindin-1 promotes neurite outgrowth by binding necdin and recruiting it to the cytoplasm, thereby relieving necdin's repression of p53 transcriptional activity. p53 target genes coronin 1b and rab13 are required for neurite outgrowth; knockdown of dysbindin-1 reduces their expression similar to p53 knockdown. Overexpression of p53 rescues the neurite outgrowth defect caused by dysbindin-1 knockdown. In sdy mouse brains, p21, coronin 1b, and Rab13 levels are reduced. Yeast two-hybrid (necdin identification), co-immunoprecipitation, siRNA knockdown, overexpression rescue, primary cortical neuron culture from sdy mice Molecular psychiatry Medium 21502952
2012 SILAC quantitative proteomics identified 24 proteins that associate with the BLOC-1 complex (containing dysbindin), including the COG complex (a Golgi apparatus tether) and antioxidant enzymes peroxiredoxins 1-2. Many of these interactors were altered in content/distribution in BLOC-1-deficient cells or tissues. SILAC quantitative proteomics, genetic analyses in dysbindin-null mice The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 22423091
2011 Drosophila dysbindin (Ddysb) regulates glutamatergic and dopaminergic functions through two independent mechanisms: reduced Ddysb in presynaptic neurons suppresses glutamatergic synaptic transmission (causing memory impairment), while reduced Ddysb in glial cells causes hyperdopaminergic activity by altering expression of dopamine metabolic enzyme Ebony (leading to abnormal locomotion and mating orientation). Cell-type-specific RNAi in Drosophila, electrophysiology, behavioral analysis, Ebony expression analysis Proceedings of the National Academy of Sciences of the United States of America High 22049342
2013 Dysbindin-1 null mice show reduced NMDAR-dependent synaptic potentiation in CA1, which is rescued by bath application of the NMDAR co-agonist glycine (10 μM). Dysbindin-null mice also exhibit deficits in contextual fear conditioning, indicating impaired hippocampal memory processes linked to NMDAR hypofunction. Field electrophysiology in acute hippocampal slices, pharmacological rescue with glycine, fear conditioning behavioral test Hippocampus Medium 24446171
2013 Dysbindin-null mutant mice show decreased ready-releasable pool of synaptic vesicles, decreased quantal size, decreased release probability, and deficits in endo- and exocytosis rate in prefrontal cortical neurons. Additionally, dysbindin-null mice show decreased intracellular calcium, reduced expression of L- and N-type Ca2+ channels, and reduced levels of synaptic vesicle trafficking and priming proteins. Electrophysiology, vesicle imaging, calcium imaging, Western blot in dysbindin-null mice Schizophrenia research Medium 23473812
2014 Dysbindin is required to stabilize dendritic protrusions. In dysbindin-null neurons, dendritic protrusions are hyperactive in formation, retraction, and conversion between types. This hyperactivity is attributed in part to decreased CaMKIIα activity resulting from increased inhibition of CaMKIIα by Abi1 (which accumulates when dysbindin is absent). Time-lapse imaging in hippocampal neurons, genetic null model, CaMKIIα activity assay The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 25297099
2014 Dysbindin-1C isoform (but not dysbindin-1A) is specifically localized in hilar glutamatergic mossy cells of the dentate gyrus. Dysbindin-1C deficiency leads to a decrease in mossy cells, which causes delayed maturation of newborn neurons in the dentate gyrus, indicating an isoform-specific, non-cell-autonomous role in adult hippocampal neurogenesis. Isoform-specific localization, comparison of sdy (1A+1C null) vs. muted (1A destabilized, 1C intact) mice, adult neurogenesis assays The Journal of biological chemistry Medium 25157109
2015 Dysbindin/BLOC-1 and ATP7A (copper transporter mutated in Menkes disease) genetically and biochemically interact. Loss of dysbindin/BLOC-1 alters the transcriptional profile of copper-regulatory and dependent factors in the hippocampus of null mice and alters susceptibility to toxic copper challenges in mammalian cells and Drosophila, without affecting baseline tissue copper content. Co-immunoprecipitation, genetic epistasis in Drosophila and mice, transcriptional profiling, copper toxicity assay Human molecular genetics Medium 26199316
2015 Dysbindin-1 loss reduces BDNF exocytosis from cortical excitatory neurons. This reduction in BDNF exocytosis transsynaptically reduces the number of inhibitory synapses formed on excitatory neurons. Exogenous BDNF application rescues the inhibitory synaptic deficits caused by reduced dysbindin-1 in cultured and slice cultures. TIRF microscopy for BDNF exocytosis, whole-cell recordings, immunohistochemistry, pharmacological rescue in dysbindin mutant mice Biological psychiatry High 26386481
2015 N-ethylmaleimide-sensitive factor (NSF) is a binding partner of dysbindin/BLOC-1; NSF content is downregulated in dysbindin/BLOC-1-deficient neuroectodermal cells and iPSC-derived human neurons. Human dysbindin/BLOC-1 co-precipitates with NSF. In Drosophila, the dysbindin mutant phenotype of impaired homeostatic synaptic plasticity is fully rescued by presynaptic expression of either dysbindin or NSF. Quantitative proteomics, co-immunoprecipitation, Drosophila genetic rescue experiment, electrophysiology The Journal of neuroscience : the official journal of the Society for Neuroscience High 25972187
2015 Loss of dysbindin-1 impairs hippocampal group 1 metabotropic glutamate receptor (mGluRI) function: mGluRI agonist (DHPG)-induced ERK1/2 phosphorylation is markedly reduced in sdy mouse hippocampal synaptosomes. DHPG-induced LTD at CA1 synapses is also significantly reduced. A positive allosteric modulator of mGluR5 (CDPPB) rescues short-term object recognition and spatial learning deficits in sdy mice. Synaptoneurosomes from sdy mice, Western blot for ERK1/2 phosphorylation, field electrophysiology for LTD, pharmacological rescue with CDPPB Frontiers in behavioral neuroscience Medium 25859193
2015 Drosophila BLOC-1 (containing dysbindin) is present in neurons and regulates synaptic output, morphology, and homeostatic plasticity. Homozygous loss-of-function alleles of dysb or Blos1, or compound heterozygotes, impair neurotransmitter release, synapse morphology, and homeostatic plasticity at the larval NMJ and impair olfactory habituation. Phenotypes are differentially sensitive to genetic dosage of BLOC-1 alleles. Drosophila genetics, electrophysiology at NMJ, behavioral assay, biochemical confirmation of BLOC-1 in neurons The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 25568125
2016 The Arp2/3 actin polymerization complex is identified downstream of dysbindin/BLOC-1 by quantitative proteomics; Arp2/3 subunits are downregulated by BLOC-1 loss of function. Arp2/3, dysbindin, and BLOC-1 subunits biochemically and genetically interact, modulating Drosophila synapse morphology and homeostatic plasticity. Loss of BLOC-1 affects actin dynamics in early endosomes. Quantitative mass spectrometry, co-immunoprecipitation, genetic interaction in Drosophila, actin dynamics assay The Journal of neuroscience : the official journal of the Society for Neuroscience High 27927957
2017 TRIM24 is identified as a novel dysbindin binding partner in cardiac muscle (yeast two-hybrid + co-immunoprecipitation). TRIM24 protects dysbindin from TRIM32-mediated ubiquitin-dependent degradation, promoting SRF-dependent hypertrophic signaling. TRIM32 degrades dysbindin in cardiomyocytes and also promotes apoptosis via p53 and caspase-3/-7 activation. Yeast two-hybrid, co-immunoprecipitation, co-immunostaining, overexpression/knockdown in neonatal cardiomyocytes, SRF reporter assay The Journal of biological chemistry Medium 28465353
2018 Genetic variations reducing dysbindin-1 expression interact with antipsychotic drugs to improve executive functions in schizophrenia. The molecular mechanism involves an imbalance between short and long isoforms of dopamine D2 receptors, leading to enhanced presynaptic D2 function in the prefrontal cortex, as demonstrated in postmortem human brains and dysbindin-deficient mice treated with antipsychotics. Postmortem human brain analysis (D2R isoforms), genetically modified mice, pharmacological treatment, ex vivo and in vivo analyses Nature communications Medium 29891954
2015 Dysbindin-1B aggregates into cell-invasive deposits and propagates between neurons via exosome-mediated transmission. Dysbindin-1B aggregates are neurotoxic and exert toxic effects on recipient neurons distant from the initial aggregation site through exosomal spread in mouse brain. Overexpression in mice, exosome isolation, neuronal toxicity assay, live imaging Neuroscience Low 25704251

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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). Nature genetics 352 12923531
2002 Support for association of schizophrenia with genetic variation in the 6p22.3 gene, dysbindin, in sib-pair families with linkage and in an additional sample of triad families. American journal of human genetics 291 12474144
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.) 179 19965435
2003 The DTNBP1 (dysbindin) gene contributes to schizophrenia, depending on family history of the disease. American journal of human genetics 160 14618545
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 128 18504299
2006 Dysbindin-1 is a synaptic and microtubular protein that binds brain snapin. Human molecular genetics 127 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
2009 The dysbindin-containing complex (BLOC-1) in brain: developmental regulation, interaction with SNARE proteins and role in neurite outgrowth. Molecular psychiatry 124 19546860
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 116 20956979
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
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
2009 Neurobehavioral abnormalities in the dysbindin-1 mutant, sandy, on a C57BL/6J genetic background. Genes, brain, and behavior 85 19220483
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
2012 Quantitative proteomic and genetic analyses of the schizophrenia susceptibility factor dysbindin identify novel roles of the biogenesis of lysosome-related organelles complex 1. The Journal of neuroscience : the official journal of the Society for Neuroscience 74 22423091
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
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 62 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 Hyperactivation of midbrain dopaminergic system in schizophrenia could be attributed to the down-regulation of dysbindin. Biochemical and biophysical research communications 61 16701550
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
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 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
2005 Identifying potential risk haplotypes for schizophrenia at the DTNBP1 locus in Han Chinese and Scottish populations. Molecular psychiatry 48 16044171
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
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
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 44 25568125
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
2006 Association of the dysbindin gene with bipolar affective disorder. The American journal of psychiatry 41 16946192
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
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
2017 Dysbindin-1 Involvement in the Etiology of Schizophrenia. International journal of molecular sciences 37 28937620
2010 Impact of schizophrenia-risk gene dysbindin 1 on brain activation in bilateral middle frontal gyrus during a working memory task in healthy individuals. Human brain mapping 37 19650139
2008 Dysbindin engages in c-Jun N-terminal kinase activity and cytoskeletal organization. Biochemical and biophysical research communications 37 19094965
2009 Mixture model clustering of phenotype features reveals evidence for association of DTNBP1 to a specific subtype of schizophrenia. Biological psychiatry 35 19782967
2010 Cytosolic protein interactions of the schizophrenia susceptibility gene dysbindin. Journal of neurochemistry 34 20236384
2010 Dysfunction of dopamine release in the prefrontal cortex of dysbindin deficient sandy mice: an in vivo microdialysis study. Neuroscience letters 31 20045719
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 DTNBP1, NRG1, DAOA, DAO and GRM3 polymorphisms and schizophrenia: an association study. Neuropsychobiology 31 19439994
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 Dysbindin-1 loss compromises NMDAR-dependent synaptic plasticity and contextual fear conditioning. Hippocampus 28 24446171
2008 Comprehensive analysis of tagging sequence variants in DTNBP1 shows no association with schizophrenia or with its composite neurocognitive endophenotypes. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 28 18314870
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
2013 Potential molecular mechanisms for decreased synaptic glutamate release in dysbindin-1 mutant mice. Schizophrenia research 27 23473812
2009 Genetic variation in schizophrenia-risk-gene dysbindin 1 modulates brain activation in anterior cingulate cortex and right temporal gyrus during language production in healthy individuals. NeuroImage 27 19497374
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 The schizophrenia susceptibility gene dysbindin regulates dendritic spine dynamics. The Journal of neuroscience : the official journal of the Society for Neuroscience 26 25297099
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
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 25 25157109
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
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 24 23364359
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
2015 Constant light uncovers behavioral effects of a mutation in the schizophrenia risk gene Dtnbp1 in mice. Behavioural brain research 22 25677649
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
2018 Impaired copper transport in schizophrenia results in a copper-deficient brain state: A new side to the dysbindin story. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry 21 30230404
2015 Propagation of dysbindin-1B aggregates: exosome-mediated transmission of neurotoxic deposits. Neuroscience 21 25704251
2011 Dysbindin-1 gene contributes differentially to early- and adult-onset forms of functional psychosis. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 21 21305691
2010 A genetic variation in the dysbindin gene (DTNBP1) is associated with memory performance in healthy controls. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry 21 19353385