| 001 | 62865 | ||
| 005 | 20200423204620.0 | ||
| 024 | 7 | _ | |a pmid:18400883 |2 pmid |
| 024 | 7 | _ | |a 10.1523/JNEUROSCI.5389-07.2008 |2 DOI |
| 024 | 7 | _ | |a WOS:000255012400003 |2 WOS |
| 024 | 7 | _ | |a 2128/20509 |2 Handle |
| 024 | 7 | _ | |a altmetric:3455246 |2 altmetric |
| 037 | _ | _ | |a PreJuSER-62865 |
| 041 | _ | _ | |a eng |
| 082 | _ | _ | |a 590 |
| 084 | _ | _ | |2 WoS |a Neurosciences |
| 100 | 1 | _ | |a Leliveld, S. R. |b 0 |u FZJ |0 P:(DE-Juel1)VDB72260 |
| 245 | _ | _ | |a Insolubility of disrupted-in-schizophrenia 1 disrupts oligomer-dependent interactions with nuclear distribution element 1 and is associated with sporadic mental disease |
| 260 | _ | _ | |a Washington, DC |b Soc. |c 2008 |
| 300 | _ | _ | |a 3839 - 3845 |
| 336 | 7 | _ | |a Journal Article |0 PUB:(DE-HGF)16 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a article |2 DRIVER |
| 440 | _ | 0 | |a Journal of Neuroscience |x 0270-6474 |0 3603 |y 15 |v 28 |
| 500 | _ | _ | |a Record converted from VDB: 12.11.2012 |
| 520 | _ | _ | |a Disrupted-in-schizophrenia 1 (DISC1) and other genes have been identified recently as potential molecular players in chronic psychiatric diseases such as affective disorders and schizophrenia. A molecular mechanism of how these genes may be linked to the majority of sporadic cases of these diseases remains unclear. The chronic nature and irreversibility of clinical symptoms in a subgroup of these diseases prompted us to investigate whether proteins corresponding to candidate genes displayed subtle features of protein aggregation. Here, we show that in postmortem brain samples of a distinct group of patients with phenotypes of affective disorders or schizophrenia, but not healthy controls, significant fractions of DISC1 could be identified as cold Sarkosyl-insoluble protein aggregates. A loss-of-function phenotype could be demonstrated for insoluble DISC1 through abolished binding to a key DISC1 ligand, nuclear distribution element 1 (NDEL1): in human neuroblastoma cells, DISC1 formed expression-dependent, detergent-resistant aggregates that failed to interact with endogenous NDEL1. Recombinant (r) NDEL1 expressed in Escherichia coli selectively bound an octamer of an rDISC1 fragment but not dimers or high molecular weight multimers, suggesting an oligomerization optimum for molecular interactions of DISC1 with NDEL1. For DISC1-related sporadic psychiatric disease, we propose a mechanism whereby impaired cellular control over self-association of DISC1 leads to excessive multimerization and subsequent formation of detergent-resistant aggregates, culminating in loss of ligand binding, here exemplified by NDEL1. We conclude that the absence of oligomer-dependent ligand interactions of DISC1 can be associated with sporadic mental disease of mixed phenotypes. |
| 536 | _ | _ | |a Funktion und Dysfunktion des Nervensystems |c P33 |2 G:(DE-HGF) |0 G:(DE-Juel1)FUEK409 |x 0 |
| 588 | _ | _ | |a Dataset connected to Web of Science, Pubmed |
| 650 | _ | 2 | |2 MeSH |a Animals |
| 650 | _ | 2 | |2 MeSH |a Brain Chemistry |
| 650 | _ | 2 | |2 MeSH |a Cadaver |
| 650 | _ | 2 | |2 MeSH |a Carrier Proteins: metabolism |
| 650 | _ | 2 | |2 MeSH |a Cell Line, Tumor |
| 650 | _ | 2 | |2 MeSH |a Drug Interactions |
| 650 | _ | 2 | |2 MeSH |a Escherichia coli: metabolism |
| 650 | _ | 2 | |2 MeSH |a Humans |
| 650 | _ | 2 | |2 MeSH |a Ligands |
| 650 | _ | 2 | |2 MeSH |a Mice |
| 650 | _ | 2 | |2 MeSH |a Mice, Transgenic |
| 650 | _ | 2 | |2 MeSH |a Mood Disorders: genetics |
| 650 | _ | 2 | |2 MeSH |a Mood Disorders: metabolism |
| 650 | _ | 2 | |2 MeSH |a Nerve Tissue Proteins: chemistry |
| 650 | _ | 2 | |2 MeSH |a Nerve Tissue Proteins: metabolism |
| 650 | _ | 2 | |2 MeSH |a Phenotype |
| 650 | _ | 2 | |2 MeSH |a Proteome: isolation & purification |
| 650 | _ | 2 | |2 MeSH |a Recombinant Proteins: metabolism |
| 650 | _ | 2 | |2 MeSH |a Schizophrenia: genetics |
| 650 | _ | 2 | |2 MeSH |a Schizophrenia: metabolism |
| 650 | _ | 2 | |2 MeSH |a Solubility |
| 650 | _ | 7 | |0 0 |2 NLM Chemicals |a Carrier Proteins |
| 650 | _ | 7 | |0 0 |2 NLM Chemicals |a DISC1 protein, human |
| 650 | _ | 7 | |0 0 |2 NLM Chemicals |a Ligands |
| 650 | _ | 7 | |0 0 |2 NLM Chemicals |a NDEL1 protein, human |
| 650 | _ | 7 | |0 0 |2 NLM Chemicals |a Nerve Tissue Proteins |
| 650 | _ | 7 | |0 0 |2 NLM Chemicals |a Proteome |
| 650 | _ | 7 | |0 0 |2 NLM Chemicals |a Recombinant Proteins |
| 650 | _ | 7 | |a J |2 WoSType |
| 653 | 2 | 0 | |2 Author |a psychiatric disease |
| 653 | 2 | 0 | |2 Author |a depression |
| 653 | 2 | 0 | |2 Author |a bipolar disorder |
| 653 | 2 | 0 | |2 Author |a multimerization |
| 653 | 2 | 0 | |2 Author |a protein conformational disease |
| 653 | 2 | 0 | |2 Author |a protein aggregation |
| 700 | 1 | _ | |a Bader, V. |b 1 |0 P:(DE-HGF)0 |
| 700 | 1 | _ | |a Hendriks, P. |b 2 |0 P:(DE-HGF)0 |
| 700 | 1 | _ | |a Prikulis, I. |b 3 |0 P:(DE-HGF)0 |
| 700 | 1 | _ | |a Sajnani, G. |b 4 |0 P:(DE-HGF)0 |
| 700 | 1 | _ | |a Requena, J. R. |b 5 |0 P:(DE-HGF)0 |
| 700 | 1 | _ | |a Korth, C. |b 6 |0 P:(DE-HGF)0 |
| 773 | _ | _ | |a 10.1523/JNEUROSCI.5389-07.2008 |g Vol. 28, p. 3839 - 3845 |p 3839 - 3845 |q 28<3839 - 3845 |0 PERI:(DE-600)1475274-8 |t The @journal of neuroscience |v 28 |y 2008 |x 0270-6474 |
| 856 | 7 | _ | |u http://dx.doi.org/10.1523/JNEUROSCI.5389-07.2008 |
| 856 | 4 | _ | |u https://juser.fz-juelich.de/record/62865/files/3839.full.pdf |y OpenAccess |
| 856 | 4 | _ | |u https://juser.fz-juelich.de/record/62865/files/3839.full.pdf?subformat=pdfa |x pdfa |y OpenAccess |
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| 914 | 1 | _ | |y 2008 |
| 915 | _ | _ | |a OpenAccess |0 StatID:(DE-HGF)0510 |2 StatID |
| 915 | _ | _ | |a JCR/ISI refereed |0 StatID:(DE-HGF)0010 |
| 920 | 1 | _ | |k INB-2 |l Molekulare Biophysik |d 31.12.2008 |g INB |0 I:(DE-Juel1)VDB805 |x 0 |
| 970 | _ | _ | |a VDB:(DE-Juel1)99748 |
| 980 | 1 | _ | |a FullTexts |
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| 981 | _ | _ | |a I:(DE-Juel1)ICS-6-20110106 |
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