Recombinant Mouse Dysbindin (Dtnbp1)

1. Multilevel ex vivo and in vivo analyses in genetically modified mice demonstrate that interaction between antipsychotics and dysbindin-1 is mediated by an imbalance between the short and long isoforms of dopamine D2 receptors, leading to enhanced presynaptic D2 function within the prefrontal cortex. PMID: 29891954
2. Nuclear SREBP1 is dramatically reduced in dysbindin-1 knockout mice. PMID: 26873854
3. loss of DTNBP1 in pyramidal neurons diminished activity-dependent secretion of brain-derived neurotrophic factor (BDNF). PMID: 27330059
4. Dysbindin-1 modulates thus D2 and D3 receptor signaling, supporting a link to schizophrenia PMID: 26685100
5. Results indicate that perturbations downstream of DTNBP1, confer susceptibility to copper, a metal that in excess is a neurotoxin and whose depletion constitutes a micronutrient deficiency. PMID: 26199316
6. Results suggest that Dtnbp1 deficiency may lead to increased vulnerability to schizophrenia under environmental conditions where circadian rhythms are altered PMID: 25677649
7. Snapin-dysbindin interaction regulates synaptic vesicle positional priming through BLOC-1/AP-3-dependent sorting. PMID: 26108535
8. Dysbindin has three isoforms associating with different complexes in the P2 fraction of mouse brain. PMID: 25198678
9. Dysbindin-1C deficiency causes impaired autophagy, which is likely implicated in the pathogenesis of schizophrenia. PMID: 25619597
10. The neurite outgrowth defect induced by knockdown of DISC1 was partially reversed by coexpression of dysbindin. PMID: 25635053
11. dysbindin-1C, rather than dysbindin-1A, regulates adult hippocampal neurogenesis in a non-cell autonomous manner PMID: 25157109
12. loss of function mutations in the genes encoding dysbindin and its interacting BLOC-1 subunits PMID: 24713699
13. These data confirm at the level of mouse working memory and human working memory-associated physiology a genetic interaction between COMT and DTNBP1. PMID: 24145376
14. Mecp2 regulates the expression of components belonging to the dysbindin interactome PMID: 23750231
15. the results of this study indicated that a loss of dysbindin-1 impairs hippocampal plasticity which may, in part, explain the role dysbindin-1 plays in the cognitive impairments of schizophrenia. PMID: 24446171
16. Loss of dysbindin led to enhanced CA3-CA1 AMPAR-mediated synaptic transmission and long term plasticity in hippocampal slices. PMID: 24321452
17. a novel cardiac role of Dysbindin in the activation of RhoA-SRF and MEK1-ERK1 signaling pathways and in the induction of cardiac hypertrophy, is reported. PMID: 24385487
18. This study demonistrated that the dysbindin-1 null mice show decreases in the [Ca(2+)]i,expression of L- and N-type Ca(2+)channels and several proteins involved in synaptic vesicle trafficking and priming. PMID: 23473812
19. Dys-/- mice exhibited increased compulsive and impulsive behaviors compared to control littermates suggesting the inability to suppress incorrectly-timed responses underlies their increased time to acquisition. PMID: 23261874
20. dysbindin and its associated complex sort cargoes from cell bodies to the synapse. PMID: 21998198
21. The results of this study indicate that genetically induced reductions in dysbindin can impact cognition via an effect on DA/D2 mechanisms in the rodent homolog of the dorsolateral PFC PMID: 20956979
22. Dysbindin-1 recruits necdin to the cytoplasm, attenuating the repressive effects of necdin on p53 transcriptional activity. Dysbindin-1 has an important role in neurite outgrowth through its regulation of p53's transcriptional activity. PMID: 21502952
23. Dysbindin-1 mutant mice implicate reduced fast-phasic inhibition as a final common disease mechanism in schizophrenia. PMID: 21969553
24. dysbindin plays a role during differentiation process in the adult hippocampal neurogenesis PMID: 21267465
25. These results suggest that the dysbindin deficiency could be an essential genetic factor that causes synaptic hypersensitivity to dopamine and serotonin. PMID: 21448290
26. Decreases in dysbindin are associated with specific decreases in NMDA-evoked currents in prefrontal pyramidal neurons, and decreases in NR1 expression, the degree of NR1 expression correlates with spatial working memory performance. PMID: 21035792
27. Sdy mouse, which has a deletion in the Dtnbp1 gene, showed impaired long-term memory retention and working memory. PMID: 18945333
28. the nucleocytoplasmic shuttling of dysbindin-1 regulates synapsin I expression and thus may be involved in the pathogenesis of schizophrenia. PMID: 20921223
29. findings suggest that abnormal expression of MARCKS via dysfunction of Dysbindin might cause impairment of neural transmission and abnormal synaptogenesis PMID: 20098743
30. results suggest that dysbindin may have a role in the regulation of depolarization-evoked dopamine release in the prefrontal cortex and in the development of behavioral sensitization induced by repeated methamphetamine treatment PMID: 20045719
31. dysbindin controls hippocampal LTP by selective regulation of the surface expression of NR2A PMID: 19955431
32. dysbindin potently regulates excitatory transmission in the prefrontal cortex, potentially through a pre-synaptic mechanism, and consequently modulates cognitive functions depending on this brain region PMID: 19641486
33. In mdx mice, in which dystrophin is not expressed, there is a dramatic increase in dysbindin-immunoreactive glomeruli in the posterior cerebellar vermis. Terminal field topography is disrupted, replacing the stripes by a homogeneous distribution PMID: 12878699
34. sdy mutant mouse expresses no dysbindin protein owing to a deletion in the gene Dtnbp1 (encoding dysbindin) and that mutation of the human ortholog DTNBP1 causes Hermansky-Pudlak syndrome type 7 PMID: 12923531
35. Dysbindin binds to myospryn in muscle PMID: 14688250
36. Dysbindin appears to have novel neuronal functions. PMID: 15345706
37. results demonstrate that snapin is a binding partner of dysbindin-1 in vitro and in the brain; both dysbindin-1 and snapin are concentrated in tissue enriched in synaptic vesicle membranes and less commonly in postsynaptic densities PMID: 16980328
38. These data demonstrate that DA turnover in the specific regions of the brain of the Sdy mouse was increased. PMID: 17548156
39. As dysbindin has lately been shown to be involved in membrane biogenesis and fusion, a key process for acrosome formation, we propose that RNF151 may play a role in acrosome formation. PMID: 17577571
40. dysbindin functions to regulate exocytosis and vesicle biogenesis in endocrine cells and neurons PMID: 18504299
41. Behavioral analyses on homozygous sandy (sdy) mice, which lack dysbindin-1 owing to a deletion in the Dtnbp1 gene, were performed. PMID: 18555792
42. We further characterized that a 30-residue peptide in dysbindin (90-119 amino acids) mediated the interaction with snapin. Our results suggest that the destabilization of snapin in sdy mice may lead to abnormal neurotransmission and abnormal behaviors. PMID: 18774265
43. Homozygous and heterozygous dysbindin-1 deficient sandy mice show a lack of locomotor habituation in a repeated testing. PMID: 18984010
44. These findings suggest that dysbindin plays a key role in coordinating JNK signaling and actin cytoskeleton required for neural development. PMID: 19094965
45. decreased dysbindin-1 in the sandy mouse may model certain aspects of cognition and behavior relevant to schizophrenia PMID: 19220483
46. Dysbindin appears to participate in the exocytosis or sorting of the synaptic vesicle via direct interaction with the AP-3 complex PMID: 19428785
47. Immunogold electron microscopy revealed that dysbindin signal was observed at the inside surface of plasma membrane of glial endfeet which surrounded the brain capillary endothelial cells and pericytes. PMID: 19495999
48. dysbindin regulates prefrontal cortex function by facilitating D2-mediated modulation of GABAergic function. PMID: 19887632

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Defects in Dtnbp1 are the cause of the sandy (sdy) mutant phenotype, a model for human Hermansky-Pudlak syndrome (HPS). Sdy mice lack dysbindin expression; they have a characteristic sandy coat color and have much fewer melanosomes in the retinal pigment epithelium and choroid. They are fully viable, but present behavioral abnormalities. They have prolonged bleeding times due to platelet storage pool deficiency, and lysosomal storage defects. The number of electron-opaque platelet dense granules is severely reduced, and the platelet serotonin content is strongly reduced. Secretion of lysosomal enzymes from kidney and from thrombin-stimulated platelets is depressed 2- and 3-fold, and ceroid pigment is present in kidney. Sandy mice also display impaired long-term memory retention and working memory and schizophrenia-like behavioral abnormalities. Vesicle morphology and kinetics of transmitter release are affected in both neuroendocrine cells and hippocampal synapses, characterized by larger vesicle size, slower quantal release, fewer release events and reduced readily releasable pool (RRP). Expression levels of SYN1 are lower in both the cortex and the hippocampal formation (HF).

[Isoform 1]: Cytoplasm. Cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side. Endosome membrane; Peripheral membrane protein; Cytoplasmic side. Melanosome membrane; Peripheral membrane protein; Cytoplasmic side. Cell junction, synapse, postsynaptic density. Endoplasmic reticulum. Nucleus.; [Isoform 3]: Cytoplasm. Cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side. Cytoplasmic vesicle, secretory vesicle, synaptic vesicle membrane; Peripheral membrane protein; Cytoplasmic side. Endosome membrane; Peripheral membrane protein; Cytoplasmic side. Melanosome membrane; Peripheral membrane protein; Cytoplasmic side. Cell junction, synapse, postsynaptic cell membrane. Endoplasmic reticulum.

Dysbindin family

Detected in brain, in hippocampus and dentate gyrus neurons. Detected at axon bundles and axon terminals, notably in the cerebellum and hippocampus. Detected in neuropil in hippocampus, lateral septum, basal ganglia and substantia nigra. Highly expressed

KEGG: mmu:94245

STRING: 10090.ENSMUSP00000072170

UniGene: Mm.352311