Disrupted-in-schizophrenia 1 (DISC1) Regulates Dysbindin Function by Enhancing Its Stability

Lee, Seol-Ae; Kim, Seong-Mo; Suh, Bo Kyoung; Sun, Haiyan; Park, Young-Un; Hong, Ji-Ho; Park, Cana; Nguyen, Minh Dang; Nagata, Koh‐ichi; Yoo, Joo‐Yeon

doi:10.1074/jbc.m114.614750

Cited by 19 publications

(21 citation statements)

References 53 publications

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“…CAD cells were transfected with pmCherry-N1 (Clontech) and FITC-conjugated siRNAs targeting mouse REST or TRIM28 using Lipofectamine 2000 as described previously68. At 48 h post transfection, cells were detached and seeded again onto plates and then cultured for 48 h in serum-free DMEM media for differentiation.…”

Section: Methodsmentioning

confidence: 99%

Interactomic analysis of REST/NRSF and implications of its functional links with the transcription suppressor TRIM28 during neuronal differentiation

Lee

Park

Haddad

et al. 2016

Sci Rep

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RE-1 silencing transcription factor (REST) is a transcriptional repressor that regulates gene expression by binding to repressor element 1. However, despite its critical function in physiology, little is known about its interaction proteins. Here we identified 204 REST-interacting proteins using affinity purification and mass spectrometry. The interactome included proteins associated with mRNA processing/splicing, chromatin organization, and transcription. The interactions of these REST-interacting proteins, which included TRIM28, were confirmed by co-immunoprecipitation and immunocytochemistry, respectively. Gene Ontology (GO) analysis revealed that neuronal differentiation-related GO terms were enriched among target genes that were co-regulated by REST and TRIM28, while the level of CTNND2 was increased by the knockdown of REST and TRIM28. Consistently, the level of CTNND2 increased while those of REST and TRIM28 decreased during neuronal differentiation in the primary neurons, suggesting that CTNND2 expression may be co-regulated by both. Furthermore, neurite outgrowth was increased by depletion of REST or TRIM28, implying that reduction of both REST and TRIM28 could promote neuronal differentiation via induction of CTNND2 expression. In conclusion, our study of REST reveals novel interacting proteins which could be a valuable resource for investigating unidentified functions of REST and also suggested functional links between REST and TRIM28 during neuronal development.

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Section: Methodsmentioning

confidence: 99%

Interactomic analysis of REST/NRSF and implications of its functional links with the transcription suppressor TRIM28 during neuronal differentiation

Lee

Park

Haddad

et al. 2016

Sci Rep

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“…DISC1 codes for a major protein of about 100 kDa and various, yet incompletely characterized isoforms generated by alternative splicing [26]. Many studies have demonstrated that DISC1 plays important roles during neurodevelopment, including neuronal proliferation, neurite outgrowth, neuronal migration, and synapse formation, all implicated in the pathophysiology of schizophrenia (reviewed in [27]). Furthermore, genetic variants of DISC1 were shown to be associated with the hippocampal volume [28], cortical thickness [29], and prefrontal-associated cognition [25].…”

Section: Introductionmentioning

confidence: 99%

Increased density of DISC1-immunoreactive oligodendroglial cells in fronto-parietal white matter of patients with paranoid schizophrenia

Bernstein

Jauch

Dobrowolny

et al. 2015

Eur Arch Psychiatry Clin Neurosci

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Profound white matter abnormalities have repeatedly been described in schizophrenia, which involve the altered expression of numerous oligodendrocyte-associated genes. Transcripts of the disrupted-in-schizophrenia 1 (DISC1) gene, a key susceptibility factor in schizophrenia, have recently been shown to be expressed by oligodendroglial cells and to negatively regulate oligodendrocyte differentiation and maturation. To learn more about the putative role(s) of oligodendroglia-associated DISC1 in schizophrenia, we analyzed the density of DISC1-immunoreactive oligodendrocytes in the fronto-parietal white matter in postmortem brains of patients with schizophrenia. Compared with controls (N = 12) and cases with undifferentiated/residual schizophrenia (N = 6), there was a significantly increased density of DISC1-expressing glial cells in paranoid schizophrenia (N = 12), which unlikely resulted from neuroleptic treatment. Pathophysiologically, over-expression of DISC1 protein(s) in white matter oligodendrocytes might add to the reduced levels of two myelin markers, 2',3'-cyclic-nucleotide 3'-phosphodiesterase and myelin basic protein in schizophrenia. Moreover, it might significantly contribute to cell cycle abnormalities as well as to deficits in oligodendroglial cell differentiation and maturation found in schizophrenia.

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“…; Lee et al . ) and regulates a large number of cellular processes including nuclear transcription (Fu et al . ), the activity of Calmodulin‐dependent Kinase (Papaleo et al .…”

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confidence: 99%

Dysbindin‐1 modifies signaling and cellular localization of recombinant, human D₃ and D₂ receptors

Schmieg

Rocchi

Romeo

et al. 2016

Journal of Neurochemistry

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Dystrobrevin binding protein-1 (dysbindin-1), a candidate gene for schizophrenia, modulates cognition, synaptic plasticity and frontocortical circuitry and interacts with glutamatergic and dopaminergic transmission. Loss of dysbindin-1 modifies cellular trafficking of dopamine (DA) D 2 receptors to increase cell surface expression, but its influence upon signaling has never been characterized. Further, the effects of dysbindin-1 upon closely related D 3 receptors remain unexplored. Hence, we examined the impact of dysbindin-1 (isoform A) co-expression on the localization and coupling of human D 2L and D 3 receptors stably expressed in Chinese hamster ovary or SH-SY5Y cells lacking endogenous dysbindin-1. Dysbindin-1 co-transfection decreased cell surface expression of both D 3 and D 2L receptors. Address correspondence and reprint requests to Nathalie Schmieg, Institut de recherche Servier, Pole of Innovation in Neuropsychiatry, 125, chemin de Ronde, 78290 Croissy sur Seine, France. E-mail: nathalie.schmieg@crick.ac.ukAbbreviations used: AC, adenylyl cyclase; ARF6, ADP-ribosylation factor 6; BLOC-1, biogenesis of lysosome-related organelles complex 1; CHO, Chinese hamster ovary; CREB, cAMP response element-binding protein; D 2L receptor, D 2long receptor; D 2S receptor, D 2short receptor; DA, dopamine; DTNBP1, dystrobrevin binding protein 1; ERK1/2, extracellular signal-regulated kinases1/2; FCX, frontal cortex; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GASP-1, GPCR-associated sorting protein1; GSK-3b, glycogen synthase kinase 3 beta; HEK293, human embryonic kidney 293; h, human; MbCD, methylbcyclodextrine; MAPK, mitogen-activated protein kinases; PBS, phosphate buffered solution; p, phospho; Ser, serine; SPA, scintillation proximity assay; TBST, tris buffered saline with tween; Thr, threonine.

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Disrupted-in-schizophrenia 1 (DISC1) Regulates Dysbindin Function by Enhancing Its Stability

Cited by 19 publications

References 53 publications

Interactomic analysis of REST/NRSF and implications of its functional links with the transcription suppressor TRIM28 during neuronal differentiation

Interactomic analysis of REST/NRSF and implications of its functional links with the transcription suppressor TRIM28 during neuronal differentiation

Increased density of DISC1-immunoreactive oligodendroglial cells in fronto-parietal white matter of patients with paranoid schizophrenia

Dysbindin‐1 modifies signaling and cellular localization of recombinant, human D₃ and D₂ receptors

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Disrupted-in-schizophrenia 1 (DISC1) Regulates Dysbindin Function by Enhancing Its Stability

Cited by 19 publications

References 53 publications

Interactomic analysis of REST/NRSF and implications of its functional links with the transcription suppressor TRIM28 during neuronal differentiation

Interactomic analysis of REST/NRSF and implications of its functional links with the transcription suppressor TRIM28 during neuronal differentiation

Increased density of DISC1-immunoreactive oligodendroglial cells in fronto-parietal white matter of patients with paranoid schizophrenia

Dysbindin‐1 modifies signaling and cellular localization of recombinant, human D3 and D2 receptors

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Dysbindin‐1 modifies signaling and cellular localization of recombinant, human D₃ and D₂ receptors