Dataset Information

Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4: a candidate for psychiatric illnesses.

ABSTRACT: A role for the centrosome has been suggested in the pathology of major mental illnesses, especially schizophrenia (SZ).To show that pericentriolar material 1 protein (PCM1) forms a complex at the centrosome with disrupted-in-schizophrenia 1 (DISC1) and Bardet-Biedl syndrome 4 protein (BBS4), which provides a crucial pathway for cortical development associated with the pathology of SZ. To identify mutations in the PCM1 gene in an SZ population.Interaction of DISC1, PCM1, and BBS proteins was assessed by immunofluorescent staining and coimmunoprecipitation. Effects of PCM1, DISC1, and BBS on centrosomal functions and corticogenesis in vivo were tested by RNA interference. The PCM1 gene was examined by sequencing 39 exons and flanking splice sites.Probands and controls were from the collection of one of us (A.E.P.).Thirty-two probands with SZ from families that had excess allele sharing among affected individuals at 8p22 and 219 white controls.Protein interaction and recruitment at the centrosome in cells; neuronal migration in the cerebral cortex; and variant discovery in PCM1 in patients with SZ.PCM1 forms a complex with DISC1 and BBS4 through discrete binding domains in each protein. DISC1 and BBS4 are required for targeting PCM1 and other cargo proteins, such as ninein, to the centrosome in a synergistic manner. In the developing cerebral cortex, suppression of PCM1 leads to neuronal migration defects, which are phenocopied by the suppression of either DISC1 or BBS4 and are exacerbated by the concomitant suppression of both. Furthermore, a nonsense mutation that segregates with SZ spectrum psychosis was found in 1 family.Our data further support for the role of centrosomal proteins in cortical development and suggest that perturbation of centrosomal function contributes to the development of mental diseases, including SZ.

SUBMITTER: Kamiya A

PROVIDER: S-EPMC2727928 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4: a candidate for psychiatric illnesses.

Kamiya Atsushi A Tan Perciliz L PL Kubo Ken-ichiro K Engelhard Caitlin C Ishizuka Koko K Kubo Akiharu A Tsukita Sachiko S Pulver Ann E AE Nakajima Kazunori K Cascella Nicola G NG Katsanis Nicholas N Sawa Akira A

Archives of general psychiatry 20080901 9

<h4>Context</h4>A role for the centrosome has been suggested in the pathology of major mental illnesses, especially schizophrenia (SZ).<h4>Objectives</h4>To show that pericentriolar material 1 protein (PCM1) forms a complex at the centrosome with disrupted-in-schizophrenia 1 (DISC1) and Bardet-Biedl syndrome 4 protein (BBS4), which provides a crucial pathway for cortical development associated with the pathology of SZ. To identify mutations in the PCM1 gene in an SZ population.<h4>Design</h4>Int ...[more]

PMID: 18762586

Similar Datasets

Project description:Recent studies have investigated the effectiveness of aerobic exercise to improve physical and mental health outcomes in schizophrenia; however, few have explicitly explored the impact of aerobic exercise on neural microstructure, which is hypothesized to mediate the behavioral changes observed. Neural microstructure is influenced by numerous genetic factors including DISC1, which is a major molecular scaffold protein that interacts with partners like GSK3β, NDEL1, and PDE4. DISC1 has been shown to play a role in neurogenesis, neuronal migration, neuronal maturation, and synaptic signaling. As with other genetic variants that present an increased risk for disease, mutations of the DISC1 gene have been implicated in the molecular intersection of schizophrenia and numerous other major psychiatric illnesses. This study investigated whether short-term exercise recovers deficits in neural microstructure in a novel genetic Disc1 svΔ2 rat model. Disc1 svΔ2 animals and age- and sex-matched controls were subjected to a treadmill exercise protocol. Subsequent ex-vivo diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) compared neural microstructure in regions of interest (ROI) between sedentary and exercise wild-type animals and between sedentary and exercise Disc1 svΔ2 animals. Short-term exercise uncovered no significant differences in neural microstructure between sedentary and exercise control animals but did lead to significant differences between sedentary and exercise Disc1 svΔ2 animals in neocortex, basal ganglia, corpus callosum, and external capsule, suggesting a positive benefit derived from a short-term exercise regimen. Our findings suggest that Disc1 svΔ2 animals are more sensitive to the effects of short-term exercise and highlight the ameliorating potential of positive treatment interventions such as exercise on neural microstructure in genetic backgrounds of psychiatric disease susceptibility.

Dataset Information

Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4: a candidate for psychiatric illnesses.

Publications

Recruitment of PCM1 to the centrosome by the cooperative action of DISC1 and BBS4: a candidate for psychiatric illnesses.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets