Disrupted in Schizophrenia 1 and Nudel form a neurodevelopmentally regulated protein complex: implications for schizophrenia and other major neurological disorders

@article{Brandon2004DisruptedIS,
  title={Disrupted in Schizophrenia 1 and Nudel form a neurodevelopmentally regulated protein complex: implications for schizophrenia and other major neurological disorders},
  author={Nicholas J. Brandon and Emma J. Handford and Irina Schurov and Jean Christophe Rain and Michelle Pelling and B. Duran-Jimeniz and Luiz Miguel Camargo and Kevin R. Oliver and Dirk Beher and Mark S. Shearman and Paul J Whiting},
  journal={Molecular and Cellular Neuroscience},
  year={2004},
  volume={25},
  pages={42-55}
}
Disrupted In Schizophrenia 1 (DISC1) was identified as a potential susceptibility gene for schizophrenia due to its disruption by a balanced t(1;11) (q42;q14) translocation, which has been shown to cosegregate with major psychiatric disease in a large Scottish family. We have demonstrated that DISC1 exists in a neurodevelopmentally regulated protein complex with Nudel. The complex is abundant at E17 and in early postnatal life but is greatly reduced in the adult. Nudel has previously been shown… Expand
Expression of disrupted in schizophrenia 1 (DISC1) protein in the adult and developing mouse brain indicates its role in neurodevelopment
TLDR
The results suggest that DISC1 may play a critical role in brain development, consistent with the neurodevelopmental hypothesis of the etiology of schizophrenia. Expand
Molecular mechanism of schizophrenia with reference to disrupted-in-schizophrenia 1 (DISC1)
TLDR
The DISC1-Kendrin interaction is suggested to be involved in microtubule network formation and an association between single-nucleotide polymorphisms of the Kendrin gene and bipolar disease has also been suggested in a Japanese population, demonstrating that a part of bipolar disease is also a neurodevelopmental disorder. Expand
Subcellular targeting of DISC1 is dependent on a domain independent from the Nudel binding site
TLDR
The first direct evidence that DISC1 is localized to mitochondria in cultured cortical neurons that are dependent on an intact cytoskeleton is provided, Surprisingly, Nudel is seen to differentially associate with mitochondrial markers in comparison to DISC2, the first observation of such a direct relationship. Expand
Disrupted in schizophrenia 1 (DISC1): regulation of the neuropeptide VGF and role in neurodevelopment and synapses
A balanced chromosomal translocation of the Disrupted in Schizophrenia 1 (DISC1) gene in a large Scottish pedigree is linked to major depression, bipolar disorder and schizophrenia, cutting throughExpand
A schizophrenia-associated mutation of DISC1 perturbs cerebral cortex development
TLDR
It is demonstrated that DISC1 is a component of the microtubule-associated dynein motor complex and is essential for maintaining the complex at the centrosome, hence contributing to normal microtubular dynamics and suggesting that loss of DISC 1 function may underlie neurodevelopmental dysfunction in schizophrenia. Expand
DISC1-NDEL1/NUDEL protein interaction, an essential component for neurite outgrowth, is modulated by genetic variations of DISC1.
TLDR
It is shown that a specific interaction between DISC1 and nuclear distribution element-like (NDEL1/NUDEL) is required for neurite outgrowth in differentiating PC12 cells. Expand
Molecular insights into the function of the DISC locus
Disrupted-In-Schizophrenia 1 (DISCI) and Disrupted-In-Schizophrenia 2 (.DISC2) have been identified as novel candidate genes for psychiatric illness through analysis of a t(l;l 1 )(q42.1 ;ql4.3)Expand
A Review of Disrupted-in-Schizophrenia-1 (disc1): Neurodevelopment, Cognition, and Mental Conditions
TLDR
Both cytogenetic and cell biological studies consistently suggest that an overall loss of DISC1 function (either haploinsufficiency or dominant-negative, or both) may be associated with SZ and BP. Expand
Convergence of Two Independent Mental Disease Genes on the Protein Level: Recruitment of Dysbindin to Cell-Invasive Disrupted-In-Schizophrenia 1 Aggresomes
TLDR
A direct interaction of soluble and insoluble DISC1 protein with dysbindin protein demonstrates convergence of so far considered independent mental disease genes by direct molecular interaction, highlighting protein aggregation and recruitment as a biological mechanism in mental disease. Expand
Disrupted in Schizophrenia 1 Interactome: evidence for the close connectivity of risk genes and a potential synaptic basis for schizophrenia
TLDR
It is shown that dysbindin and DISC1 share common PPIs suggesting they may affect common biological processes and that the function of schizophrenia risk genes may converge. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 35 REFERENCES
Disrupted-in-Schizophrenia-1 (DISC-1): Mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth
  • Y. Ozeki, T. Tomoda, +9 authors A. Sawa
  • Medicine, Biology
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2002
TLDR
As schizophrenia is thought to reflect defects in cortical development that are determined by cytoskeletal protein activities, the cellular disturbances observed with mutant DISC-1 may be relevant to psychopathologic mechanisms. Expand
Disruption of two novel genes by a translocation co-segregating with schizophrenia.
TLDR
Observations indicate that DISC1 and DISC2 should be considered formal candidate genes for susceptibility to psychiatric illness. Expand
Neuregulin 1 and susceptibility to schizophrenia.
TLDR
The results of a genomewide scan of schizophrenia families in Iceland show that schizophrenia maps to chromosome 8p, and extensive fine-mapping of the 8p locus and haplotype-association analysis identifies neuregulin 1 (NRG1) as a candidate gene for schizophrenia. Expand
Direct association of LIS1, the lissencephaly gene product, with a mammalian homologue of a fungal nuclear distribution protein, rNUDE
TLDR
It is suggested that LIS1 functions in nuclear migration by interacting with multiple intracellular proteins in mammals by using the two‐hybrid system. Expand
NudE-L, a novel Lis1-interacting protein, belongs to a family of vertebrate coiled-coil proteins
TLDR
It is shown that mNudE-L and mLis1 are coexpressed in the postnatal and adult cerebral cortices and in the Purkinje neurons of the cerebellum, raising the possibility that phenotypic changes result, in part, from the inability of mutant Lis1 proteins to interact with the human Nud E-L polypeptide. Expand
Cloning and characterization of Disc1, the mouse ortholog of DISC1 (Disrupted-in-Schizophrenia 1).
TLDR
The mouse ortholog of DISC1 (Disrupted-in-Schizophrenia 1), a candidate gene for schizophrenia, is cloned and sequence conservation distributed across the genes and conservation of leucine zipper and coiled-coil domains in both orthologs is revealed. Expand
Genetic variation in the 6p22.3 gene DTNBP1, the human ortholog of the mouse dysbindin gene, is associated with schizophrenia.
TLDR
Family-based association analysis of 36 simple sequence-length-polymorphism markers and of 17 SNP markers implicated two regions, separated by approximately 7 Mb, that are strongly associated with schizophrenia, and it is concluded that further investigation of dysbindin is warranted. Expand
Isolation of a Miller–Dicker lissencephaly gene containing G protein β-subunit-like repeats
TLDR
The cloning of a gene (LIS-1, lissencephaly-1) in 17p13.3 that is deleted in Miller–Dieker patients is reported, identifying LIS-l as the disease gene and the deduced amino-acid sequence shows significant homology to β-subunits of heterotrimeric G proteins, suggesting that it could possibly be involved in a signal transduction pathway crucial for cerebral development. Expand
NUDEL Is a Novel Cdk5 Substrate that Associates with LIS1 and Cytoplasmic Dynein
TLDR
NUDEL is a novel LIS1-interacting protein with sequence homology to gene products also implicated in nuclear distribution in fungi and is a substrate of Cdk5, a kinase known to be critical during neuronal migration. Expand
The Lis1-Related Nudf Protein of Aspergillus nidulans Interacts with the Coiled-Coil Domain of the Nude/Ro11 Protein
TLDR
NUDF protein, the product of the nudF gene, displays 42% sequence identity with the human protein LIS1 required for neuronal migration, which strengthens the notion that these two proteins are functionally related. Expand
...
1
2
3
4
...