% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Leliveld:62865,
author = {Leliveld, S. R. and Bader, V. and Hendriks, P. and
Prikulis, I. and Sajnani, G. and Requena, J. R. and Korth,
C.},
title = {{I}nsolubility of disrupted-in-schizophrenia 1 disrupts
oligomer-dependent interactions with nuclear distribution
element 1 and is associated with sporadic mental disease},
journal = {The journal of neuroscience},
volume = {28},
issn = {0270-6474},
address = {Washington, DC},
publisher = {Soc.},
reportid = {PreJuSER-62865},
pages = {3839 - 3845},
year = {2008},
note = {Record converted from VDB: 12.11.2012},
abstract = {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.},
keywords = {Animals / Brain Chemistry / Cadaver / Carrier Proteins:
metabolism / Cell Line, Tumor / Drug Interactions /
Escherichia coli: metabolism / Humans / Ligands / Mice /
Mice, Transgenic / Mood Disorders: genetics / Mood
Disorders: metabolism / Nerve Tissue Proteins: chemistry /
Nerve Tissue Proteins: metabolism / Phenotype / Proteome:
isolation $\&$ purification / Recombinant Proteins:
metabolism / Schizophrenia: genetics / Schizophrenia:
metabolism / Solubility / Carrier Proteins (NLM Chemicals) /
DISC1 protein, human (NLM Chemicals) / Ligands (NLM
Chemicals) / NDEL1 protein, human (NLM Chemicals) / Nerve
Tissue Proteins (NLM Chemicals) / Proteome (NLM Chemicals) /
Recombinant Proteins (NLM Chemicals) / J (WoSType)},
cin = {INB-2},
ddc = {590},
cid = {I:(DE-Juel1)VDB805},
pnm = {Funktion und Dysfunktion des Nervensystems},
pid = {G:(DE-Juel1)FUEK409},
shelfmark = {Neurosciences},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:18400883},
UT = {WOS:000255012400003},
doi = {10.1523/JNEUROSCI.5389-07.2008},
url = {https://juser.fz-juelich.de/record/62865},
}